Revue des maladies respiratoires最新文献

{"title":"Difference in the inflammatory response and the corticoid response of human lung macrophages and parenchymal explants to ex-vivo cigarette smoke exposure","authors":"M. Brollo , Q. Marquant , M. Dres , H. Salvator , J. Cohen , E. Sage , M. Glorion , S. Grassin-Delyle , P. Devillier","doi":"10.1016/j.rmr.2025.02.054","DOIUrl":"10.1016/j.rmr.2025.02.054","url":null,"abstract":"<div><h3>Introduction</h3><div>COPD affects approximately 10% of the global population, with three million annual deaths. About half of COPD cases are linked to smoking, but fewer than 50% of heavy smokers develop the disease. The pharmacoloical treatment of stable COPD relies on inhaled bronchodilators and corticosteroids (ICS). The ICS use benefit in terms of lung function and exacerbation rates to both current and ex-smokers with COPD although the magnitude of the effect is lower in heavy or current smokers compared to light or ex-smokers. Cigarette smoke (CS), rich in free radicals, increases immune cells recruitment in the lungs, particularly alveolar macrophages (AM) <span><span>[1]</span></span>. Studies show varied results on the production of pro-inflammatory cytokines by AMs in smokers vs. ex- or non-smokers. Moreover, there is also a large variation in the therapeutic response to ICS in COPD patients. The lack of clear data prevents an objective view of the impact of CS on AM activation and their sensitivity to corticosteroids. This study evaluates the inflammatory responses induced by cigarette smoke extracts (CSE) on human lung macrophages in vitro and compares the effect of budesonide (BUD) under conditions exposed to CSE or LPS.</div></div><div><h3>Methods</h3><div>Lung tissues were obtained from 51 patients undergoing surgical resection for lung cancer. Peripheral tissues distant from the tumor were carefully dissected. Lung macrophages (LM) were isolated through cell adhesion from the peripheral tissue supernatant <span><span>[2]</span></span>, while parenchymal explants (PE) were prepared by dissecting 50<!--> <!-->mg fragments from the lung tissues. LM and PE were cultured separately in a warm medium containing cigarette smoke extract (CSE) at concentrations of 1%, 5%, and 7.5% for 24<!--> <!-->hours. In some experiments, LPS (10<!--> <!-->ng/mL for LM, 1<!--> <!-->μg/mL for PE) or TNF-α (10<!--> <!-->ng/mL) was added to the culture one hour after CSE stimulation. Additionally, in certain conditions, LM or PE stimulated with CSE were pre-incubated with BUD at concentrations of 10<sup>−10</sup>, 10<sup>−9</sup>, and 10<sup>−8</sup> <!-->M for 30<!--> <!-->minutes before LPS stimulation. After 24<!--> <!-->hours, supernatants were collected, and cytokine production (TNF-α, IL-6, CCL2, CCL4, CXCL1, CXCL5, and CXCL8) was measured in the LM and PE supernatants using ELISA.</div></div><div><h3>Results</h3><div>Our results show that CSE, both with and without stimulation by LPS or TNF-α, modulates the production of pro-inflammatory cytokines such as TNF-α, IL-6, CCL2, CCL4, CXCL1, CXCL5, and CXCL8 in LM. In contrast, these treatments did not have significant effects on cytokine production in the PE model. Additionally, we observed that the maximum release of pro-inflammatory cytokines by LM was higher when treated with both CSE and BUD compared to treatment with LPS and BUD.</div></div><div><h3>Conclusion</h3><div>This study has enhan","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 208-209"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Les éosinophiles humains participent à la transition épithélio-mésenchymateuse des cellules épithéliales respiratoires","authors":"A. Lebeau ,&nbsp;N. Worbe ,&nbsp;M. Brollo ,&nbsp;H. Salvator ,&nbsp;P. Devillier ,&nbsp;A. Magnan ,&nbsp;C. Tchérakian ,&nbsp;Q. Marquant","doi":"10.1016/j.rmr.2025.02.077","DOIUrl":"10.1016/j.rmr.2025.02.077","url":null,"abstract":"<div><h3>Introduction</h3><div>Les pneumopathies interstitielles diffuses (PID) sont des pathologies rares d’étiologies variées menant pour la plupart à la fibrose pulmonaire. Sur une cohorte de 220 atteints de PID fibrosantes suivis à l’hôpital Foch, 58 présentaient un taux de polynucléaires à éosinophiles (PNE) sanguin ≥<!--> <!-->0,3<!--> <!-->g/L considéré comme élevé <span><span>[1]</span></span>. Bien que le rôle des PNE dans le développement et/ou l’exacerbation des PID ait été fortement suggéré <span><span>[2]</span></span>, il n’a jamais été démontré. Nous émettons l’hypothèse que les PNE jouent un rôle dans la physiopathologie des PID. Ici, nous montrons in vitro que, selon leur statut d’activation, les PNE sont capables d’induire une transition épithélio-mésenchymateuse (TEM) sur les cellules épithéliales respiratoires.</div></div><div><h3>Méthodes</h3><div>Les PNE ont été isolés du sang de volontaires sains puis mis en coculture, après vérification de leur pureté par cytométrie en flux (90 %), avec des lignées épithéliales bronchiques et alvéolaires (respectivement les cellules BEAS-2B et A549) et des cellules épithéliales bronchiques (CEB) primaires issues de donneurs sains. Les cytokines pro-inflammatoires (IL-6, CCL2 et CCL5) et les marqueurs de la TEM (MMP9, TGFß, Fibronectine et Vimentine) ont été mesurés par ELISA et WB.</div></div><div><h3>Résultats</h3><div>La présence des PNE provoque une inflammation sur tous les types de cellules épithéliales respiratoires étudiés via une augmentation de la sécrétion d’IL-6, CCL2 et CCL5 par rapport à la condition contrôle sans PNE. Les PNE provoquent également une augmentation de MMP9, TGFb, Fibronectine et de Vimentine sur les cellules BEAS 2B et CEB mais pas sur les cellules A549.</div></div><div><h3>Conclusion</h3><div>Cette étude décrit la mise au point de la coculture de PNE avec des lignées cellulaires et des cellules primaires respiratoires. Ce modèle nous a permis d’identifier un effet pro-inflammatoire des PNE sur les cellules épithéliales respiratoires ainsi qu’une apparition des marqueurs de la TEM sur les cellules bronchiques. Dans ce contexte, il est possible que les PNE puissent constituer une caractéristique traitable pour les patients atteints de PID présentant une éosinophilie sanguine ≥<!--> <!-->0,3<!--> <!-->g/L.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 220"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are the behaviors of myogenic progenitors induced by mechanical stretch similar between the human quadriceps and diaphragm?","authors":"E. Lhospice ,&nbsp;G. Hugon ,&nbsp;F. Panaro ,&nbsp;B. Al Taweel ,&nbsp;S. Matecki ,&nbsp;G. Carnac","doi":"10.1016/j.rmr.2025.02.086","DOIUrl":"10.1016/j.rmr.2025.02.086","url":null,"abstract":"<div><h3>Introduction</h3><div>The stretch-induced behaviors of myogenic progenitors from the human diaphragm during mechanical ventilation are poorly understood. In all muscles, following injury, quiescent satellite cells (SCs) become activated, proliferate into myoblasts, and then merge and differentiate to form myotubes. Until now, SC adaptation to injury has been considered similar across various muscles. However, in animal models, transcriptional factors involved in maintaining the quiescent state, such as PAX3 and PAX7, are expressed differently between the diaphragm and quadriceps. In humans, no data currently exist to determine whether differences in stretch-induced behavior of myogenic progenitors during mechanical ventilation exist between these two muscles.</div></div><div><h3>Methods</h3><div>To address this issue, we purified and characterized human satellite cells from quadriceps and diaphragm biopsies from 11 patients. We then plan to culture these cells on a stretchable PDMS support to develop an in vitro model involving mechanical stress applied to human primary muscle-derived cells. A stretch of 12% of the initial length was applied using a FlexCell apparatus at a frequency of 0.3<!--> <!-->Hz to mimic mechanical ventilation in the ICU as showed in <span><span>Fig. 1</span></span>.</div></div><div><h3>Results</h3><div>Our preliminary results (<em>n</em> <!-->=<!--> <!-->6) show that the Pax7/Pax3 ratio at the myoblast stage, the fusion index, and the surface area at the myotube stage were higher in quadriceps compared to the diaphragm, indicating a higher quality of differentiation (<span><span>Fig. 2</span></span>). In a preliminary exploratory experiment, human diaphragm muscle cells from one patient were subjected to different stretching protocols, varying between 2 and 6 days, initiated at different stages of development. Our first results as indicated in <span><span>Fig. 3</span></span> show that the quadriceps and diaphragm cells tolerate the stretching protocol and can proliferate and differentiate under these conditions.</div></div><div><h3>Conclusion</h3><div>Our preliminary results show that a comparative study between diaphragmatic and quadriceps cells will allow us in the future to assess the sensitivity of these two cell populations to mechanical stress.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 225"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cigarette smoke on inflammatory effect of Quinolinic acid during influenza infection","authors":"G. Pamart,&nbsp;O. Le Rouzic,&nbsp;M. Pichavant,&nbsp;P. Gosset,&nbsp;O. Poulain-Godefroy","doi":"10.1016/j.rmr.2025.02.064","DOIUrl":"10.1016/j.rmr.2025.02.064","url":null,"abstract":"<div><h3>Introduction</h3><div>La bronchopneumopathie chronique obstructive (BPCO) se caractérise par une inflammation chronique et une obstruction des voies respiratoires principalement dues à l’exposition au tabac. Les patients atteints de BPCO développent fréquemment des exacerbations principalement causées par des infections, souvent virales, associées à une inflammation pulmonaire, une progression de la maladie et une augmentation de la mortalité. La voie métabolique du tryptophane, permettant la formation de NAD (Nicotinamide Adénine Dinucléotide) est également affectée par la fumée de cigarette (CS) entraînant une modification de la production de l’acide quinolinique (QA), un métabolite possédant des propriétés immunomodulatrices dont les taux sont altérés chez les patients atteints de BPCO.</div></div><div><h3>Méthode</h3><div>Notre objectif est de déterminer le rôle potentiel de la voie du tryptophane, et plus particulièrement de QA, au cours des exacerbations de la BPCO. La production de QA et l’expression des enzymes de la voie des kynurénines ont été mesurées chez des souris C57Bl6 après une semaine d’infection par le virus de la grippe H₃N2 (MOI 0,5). Des cellules épithéliales bronchiques (BEAS 2B) et des macrophages humains ont également été exposés à QA (100<!--> <!-->μM) 1 heure avant une infection par H₃N2. Les réponses antivirales et inflammatoires ont été évaluées 6 et 24<!--> <!-->heures après l’infection par RT-qPCR et dosage ELISA des cytokines.</div></div><div><h3>Résultats</h3><div>L’infection virale a stimulé l’expression de certaines enzymes de la voie des kynurénines 24<!--> <!-->h après l’infection viral, et à augmenter la concentration de QA au sein du tissu pulmonaire. La préexposition à QA augmente l’expression génique de molécules antivirales telles que IFNb et Mx1 24<!--> <!-->heures après l’infection dans les cellules BEAS 2B mais à moduler la réponse antivirale dans les macrophages en stimulant l’IFNb, mais en diminuant l’expression des récepteurs TLR. QA a également modulé l’inflammation des macrophages en stimulant l’expression et la sécrétion de molécules telles que IL6, IL8, TNFa ou encore CXCL1.</div></div><div><h3>Conclusion</h3><div>L’infection grippale induit la voie des kynurénines, et augmente la concentration de l’acide quinolinique, qui semble impacter la réponse inflammatoire et antivirale de l’épithélium respiratoire et des macrophages, suggérant son rôle au cours des exacerbations de la BPCO.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 213"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consequences of exacerbation in old rats with emphysema","authors":"Y. Colombani,&nbsp;P.E. Grillet,&nbsp;Y. Rourre,&nbsp;Q. Wynands,&nbsp;C. Roure,&nbsp;L. Alburquerque,&nbsp;F. Lopez,&nbsp;P. Pomies,&nbsp;E. Passerieux,&nbsp;A. Bourdin,&nbsp;O. Cazorla","doi":"10.1016/j.rmr.2025.02.055","DOIUrl":"10.1016/j.rmr.2025.02.055","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic Obstructive Pulmonary Disease (COPD), is marked by chronic airflow limitation due to small airway obstruction and emphysema, which involves abnormal enlargement of lung air spaces and inflammation-induced tissue destruction. COPD often coexists with cardiovascular diseases, likely due to chronic inflammation. As an age-related disease, COPD's effects are worsened with aging, intensifying both lung and systemic impacts. However, the connection between age-related emphysema and cardiac issues remains unclear, indicating a need for more research on how aging affects COPD's impact on cardiovascular health.</div></div><div><h3>Methods</h3><div>Old male Wistar rats (18 months old, <em>n</em> <!-->=<!--> <!-->9 control, 5 ELA-LPS) received weekly intra-tracheal instillations of elastase (ELA) over 4 weeks at a dose of 10<!--> <!-->U. I to induce emphysema. In the fourth week, alongside elastase, bacterial lipopolysaccharide (LPS) derived from <em>E.</em> <em>coli</em> O55 B: 5 was delivered to mimic a bacterial exacerbation. We evaluated pulmonary, cardiac and muscular functions using various in-vivo and ex-vivo methods, including cardiorespiratory tests on a treadmill, whole-body plethysmography and echocardiography. The results in aged animals were compared with those from young animals (6–7 weeks-old).</div></div><div><h3>Results</h3><div>Preliminary results revealed significant alteration in cardiac systolic function, along by morphological changes in the left ventricular posterior wall during systole and diastole, compared to the young emphysema model, where a correlation between emphysema and diastolic dysfunction was noted. Unexpectedly, there was a trend of improvement in respiratory parameters, including Peak Inspiratory Flow, Peak Expiratory Flow, and tidal volume. The cardiorespiratory performance test showed a trend towards reduced O₂ consumption and decreased exercise capacity, consistent with aging patterns. Then, the assessment of lung elastic properties (ex vivo pressure-volume curve) indicated a greater loss of pulmonary elasticity compared to the young emphysematous model. Additionally, ex vivo endurance and force tests on the soleus muscle showed a tendency toward reduced muscle endurance and strength, aligning with the findings from the treadmill test.</div></div><div><h3>Conclusion</h3><div>This multidisciplinary approach seeks to deepen our understanding of the age-related aspects of COPD-emphysema and its broader impact on human health. Initial results are promising, showing that aged rats exhibit a more severe phenotype than younger ones. Once confirmed, the underlying causes of these age-related dysfunctions compared to younger animals need to be determined to provide valuable insights into associated cardiac disorders.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 209"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Étude pilote morphologique et fonctionnelle de l’épithélium respiratoire des enfants présentant une bronchiolite oblitérante post infectieuse","authors":"J. Mazenq ,&nbsp;L. Moreno ,&nbsp;J-C. Dubus ,&nbsp;P. Chanez ,&nbsp;D. Gras","doi":"10.1016/j.rmr.2025.02.045","DOIUrl":"10.1016/j.rmr.2025.02.045","url":null,"abstract":"<div><h3>Introduction</h3><div>La bronchiolite oblitérante est une pathologie pulmonaire obstructive chronique entraînant l’oblitération des petites voies respiratoires. Il s’agit d’une pathologie rare dont la prévalence et l’incidence sont inconnues en Europe. Elle est secondaire à une infection sévère des voies respiratoires inférieures chez l’enfant dont l’<em>adénovirus</em> est l’agent causal principal. Notre objectif principal est de décrire les atteintes de l’épithélium respiratoire chez les enfants présentant une bronchiolite oblitérante post-infectieuse (PIBO).</div></div><div><h3>Méthodes</h3><div>Une étude morphologique et fonctionnelle de l’épithélium bronchique d’enfants présentant une PIBO (n<!--> <!-->=<!--> <!-->3) a été réalisée à l’aide d’un modèle d’épithélium reconstitué <em>in vitro</em> en interface air-liquide (ClinicalTrial.gov ID NCT06140901) et comparée à une population contrôle (prélèvement pulmonaire issu d’enfants nécessitant une chirurgie pour malformation pulmonaire (n<!--> <!-->=<!--> <!-->8) (CERC-SFCTCV-2023-11-21_31945). La production de médiateurs pro-inflammatoires et antiviraux susceptibles d’être impliqués dans le développement d’une PIBO a été mesurée (RT-qPCR et ELISA) à l’état basal.</div></div><div><h3>Résultats</h3><div>Des épithéliums reconstitués <em>in vitro</em> d’enfants présentant une PIBO ont été obtenus avec succès. L’étude de la cohésion cellulaire, indirectement mesurée par résistance électrique transépithéliale (TEER), est identique dans les 2 populations d’étude. Concernant l’activité ciliaire, elle est présente dans les 2 populations d’étude. L’étude des mucines (MUC5AC et MUC5B) au niveau transcrit et protéique ne retrouve pas de différence entre les cellules épithéliales issues de patient présentant une PIBO et les cellules épithéliales de la population contrôle. L’étude des récepteurs à l’<em>adénovirus</em> (CXADR et ICAM-1) au niveau transcrit ne retrouve pas de différence entre les 2 populations d’étude. À l’état basal, les transcrits IL-33 sont significativement plus faibles dans les cellules épithéliales de PIBO et ceux de TSLP semblent plus faiblement exprimés dans la PIBO comparativement à la population contrôle, alors qu’il ne semble pas y avoir de différence avec l’IL-8. Au niveau protéique, la sécrétion de TSLP est significativement plus faible dans les cellules épithéliales de PIBO, comparativement à la population contrôle, alors que l’on ne retrouve pas de différence au niveau de l’IL-8.</div></div><div><h3>Conclusion</h3><div>Ces résultats préliminaires suggèrent un faible taux d’alarmines chez les enfants atteints de PIBO, ce qui pourrait être la conséquence de leur défaut de réponse à l’infection virale initiale. Il semble important d’évaluer la réponse virale des cellules épithéliales après stimulation par l’<em>adénovirus</em>, pour mieux comprendre l’implication potentielle de l’épithélium respiratoire dans cette pathologie.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 204"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of epithelial CD146 in severe asthma","authors":"F. Lepretre ,&nbsp;L. Moreno ,&nbsp;A. Joshkon ,&nbsp;N. Bardin ,&nbsp;M. Blot-Chabaud ,&nbsp;P. Chanez ,&nbsp;D. Gras","doi":"10.1016/j.rmr.2025.02.049","DOIUrl":"10.1016/j.rmr.2025.02.049","url":null,"abstract":"<div><h3>Introduction</h3><div>Asthma is a chronic lung disease affecting 300 million people worldwide, 2-10 % of whom suffer from severe asthma. In asthma, the bronchial epithelium is dysregulated, contributing to the pathophysiology of the disease. CD₁₄₆ is an adhesion molecule that is highly expressed on all the cells from the vascular system, including endothelial cells. It is also expressed by epithelial cells, but its functions in these cells are poorly understood, as is its role in severe asthma. The aim of our study is to elucidate the role of CD₁₄₆ in the bronchial epithelium and its implication in severe asthma.</div></div><div><h3>Methods</h3><div>Bronchial epithelia of healthy controls and severe asthma patients were reconstituted in vitro using air-liquid interface culture. Measurements of CD₁₄₆ expression were made on differentiated epithelium (n<!--> <!-->=<!--> <!-->20 control and 20 severe asthma patients). Then, undifferentiated and differentiated bronchial epithelial cells were sorted based on the expression level of CD₁₄₆. The sorted undifferentiated bronchial epithelial cells were cultured and monitored during the differentiation process until obtention of a fully differentiated epithelium (n<!--> <!-->=<!--> <!-->3). The sorted differentiated bronchial epithelial cells were used to perform RNA-Seq experiments (n<!--> <!-->=<!--> <!-->4).</div></div><div><h3>Results</h3><div>We showed that CD₁₄₆ is highly expressed in severe asthma patients compared to healthy controls both at mRNA and protein levels in differentiated epithelium. Then, we have shown that CD₁₄₆ expression is not ubiquitous in the differentiated bronchial epithelium. Cell sorting and RNA-seq experiments demonstrated that CD₁₄₆ is mostly expressed by the basal epithelial cells in the differentiated epithelium. Finally, morphological analysis revealed that CD₁₄₆ seems to play a role in the bronchial epithelium differentiation process. Indeed, fully differentiated epithelium obtained from CD₁₄₆+ and CD₁₄₆− sorted undifferentiated bronchial epithelial cells were different in morphology and cell composition.</div></div><div><h3>Conclusion</h3><div>Our results suggest that CD₁₄₆ is only expressed by basal cells of the bronchial epithelium and supports an important role in the differentiation of this epithelium. Moreover, we demonstrated that CD₁₄₆is overexpressed in severe asthma, suggesting a possible role of this molecule in this disease notably during repair epithelial process.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 206"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kcnk3 deficiency aggravates right ventricular dysfunction induced by pulmonary artery banding","authors":"K. El Jekmek ,&nbsp;M. Gourmelon ,&nbsp;A. Saint-Martin Willer ,&nbsp;M. Dutheil ,&nbsp;V. Capuano ,&nbsp;O. Mercier ,&nbsp;D. Montani ,&nbsp;F. Antigny","doi":"10.1016/j.rmr.2025.02.020","DOIUrl":"10.1016/j.rmr.2025.02.020","url":null,"abstract":"<div><h3>Introduction</h3><div>Right ventricular failure (RVF) is characterized by the inability of the right ventricle (RV) to maintain adequate blood flow and is the major predictor of mortality in pulmonary arterial hypertension (PAH). PAH is defined by a mean pulmonary arterial pressure greater than 20<!--> <!-->mmHg at rest and is characterized by increased pulmonary vascular resistance, leading to right heart failure. Currently, no treatments specifically target RVF in PAH. However, slowing down the progression of RVF could delay the need for double lung transplantation and reduce PAH-related mortality. Loss-of-function mutations in the KCNK3 (Potassium channel subfamily K⁺ member 3) gene, which encodes the potassium channel known as TASK-1 (TWIK-related acid-sensitive K⁺ channel 1), have been identified in PAH patients. Our team has recently shown that KCNK3 dysfunction is involved in pulmonary vascular remodeling and contributes to the development of PAH <span><span>[1]</span></span>. They also demonstrated that reduced function and expression of KCNK3 is a hallmark of RV hypertrophy and dysfunction associated with pulmonary hypertension <span><span>[2]</span></span>.</div><div>Our objective was to investigate whether the Kcnk3 deficiency exacerbates RV remodeling in a rat model of RV dysfunction induced independently of pulmonary vascular remodeling.</div></div><div><h3>Methods</h3><div>To address this, we subjected male and female Kcnk3-deficient rats (WT, heterozygous, and homozygous) to chronic RV pressure overload by pulmonary artery banding (PAB). 4 weeks after surgery, we analyzed the consequence of Kcnk3-deficiency on RV remodeling by performing echocardiography, right heart catheterization, and RV histology.</div></div><div><h3>Results</h3><div>Our results show that rats (males and females) subjected to PAB developed RV hypertrophy and RV dysfunction. In male homozygous Kcnk3-deficient rats, PAB led to an exacerbation of RV hypertrophy, RV dilatation, and a more pronounced increase in RV systolic pressure compared to WT-PAB rats. In contrast, no difference was observed in male heterozygous Kcnk3-deficient rats compared to WT-PAB male rats. Interestingly, RV dysfunction and hypertrophy were unchanged in female homozygous Kcnk3-deficient rats subjected to PAB compared to WT-PAB female rats.</div></div><div><h3>Conclusion</h3><div>In conclusion, our results suggest that KCNK3 dysfunction is a crucial event in the physiopathology of RV failure. Further studies are needed to understand underlying molecular and cellular mechanisms and to investigate sex differences linked to Kcnk3-deficiency in these experimental conditions.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 191-192"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact de la matrice extracellulaire sur le canal mécanosensible PIEZO1 dans les cellules musculaires lisses pulmonaires","authors":"A. Leriche ,&nbsp;A. Gaubert ,&nbsp;C. Guibert ,&nbsp;T. Ducret ,&nbsp;JF. Quignard","doi":"10.1016/j.rmr.2025.02.021","DOIUrl":"10.1016/j.rmr.2025.02.021","url":null,"abstract":"<div><h3>Introduction</h3><div>L’hypertension pulmonaire est une pathologie caractérisée par un remodelage important des artères intra-pulmonaires ayant pour conséquence d’augmenter le travail cardiaque conduisant à la mort. Dans cette pathologie, les contraintes mécaniques exercées sur les cellules musculaires lisses vasculaires sont modifiées. Ces contraintes mécaniques sont perçues par des canaux ioniques membranaires mécano-sensibles tels que Piezo1 qui convertissent les différents stimuli mécaniques en influx calcique et en réponses biologiques. La rigidité de la matrice extracellulaire est une contrainte mécanique majeure et elle augmente au cours de la pathologie. Nous avons investigué les effets de la rigidité matricielle sur l’activité de Piezo1.</div></div><div><h3>Méthodes</h3><div>Des cellules musculaires lisses d’artères intra-pulmonaires ont été cultivées sur des hydrogels Bola Bis Urée (BBU) de différentes rigidités (1 à 10 KPa). Cette matrice synthétique ne contient pas de protéines pouvant interagir avec des récepteurs membranaires. La concentration calcique intracellulaire et le potentiel transmembranaire ont été mesurés grâce aux sondes fluorescentes Cal520® et FLIPR®. La prolifération cellulaire a été estimé avec CyQUANT®.</div></div><div><h3>Résultats</h3><div>Une forte rigidité matricielle (10<!--> <!-->kPa) augmente l’expression de Piezo1. Elle induit une diminution l’amplitude et un ralentissement de la cinétique des signaux calciques intracellulaires après stimulation de Piezo1 par son agoniste Yoda1. Par contre, cette forte rigidité augmente l’activité basale de Piezo1 induisant une augmentation de la concentration calcique intracellulaire basale. Elle induit aussi une dépolarisation cellulaire liée à Piezo1. L’augmentation de la rigidité induit une augmentation de la prolifération cellulaire mais qui est indépendante de Piezo1.</div></div><div><h3>Conclusion</h3><div>Ainsi la rigidité matricielle pourrait jouer un rôle de stimulus mécanique sur Piezo1 entraînant une altération de son activité en adéquation avec le contexte d’hypertension pulmonaire.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 192"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined cellular and gene therapy to treat primary ciliary dyskinesia","authors":"C. Bourdais ,&nbsp;M. Nadaud ,&nbsp;A. Coeur ,&nbsp;F. Foisset ,&nbsp;E. Ahmed ,&nbsp;I. Vachier ,&nbsp;A. Bourdin ,&nbsp;S. Assou ,&nbsp;J. De Vos","doi":"10.1016/j.rmr.2025.02.026","DOIUrl":"10.1016/j.rmr.2025.02.026","url":null,"abstract":"<div><div>Primary Ciliary Dyskinesia (PCD) is a genetic disease caused by mutations that alter cilia beating, including in the respiratory airways. This results in poor mucus clearance, severe morbidity, and increased mortality. We hypothesized that bronchial cilia beating can be restored using genetically corrected iPSC differentiated into air - liquid interface bronchial epithelium model (iALI) for autologous cell therapy. We have previously demonstrated that corrected cells derived from a PCD patient iPS line can be differentiated into iALI with functional ciliary beating. The current aim of the project is to evaluate the engraftment potential of these corrected cells and their ability to repair the pathological model post-engraftment. Several key issues need to be addressed identifying competent cells for bronchial engraftment, exploring various strategies to pre-treat the bronchial epithelium, and assessing the recovery of the ciliary beating recovery to assure bronchial repair.</div><div>Our team has established the differentiation of iPSCs into iALI. We have generated a PCD patient iPSC line using Sendai viruses, a corresponding CRISPR/Cas9 corrected cell line, as well a wild-type iPSC line and its CRISPR/Cas9 mutated counterpart. We also generated a GFP-iPSC line that expresses the fluorescent GFP protein under the human elongation factor 1 alpha promoter (EF1a), which allows us to track the engraftment of GFP-labeled bronchial stem cells in both control and mutated iALI models. Our results suggest that lung progenitors at the ventralized anterior foregut endoderm stage could be the most efficient cells for engraftment. Their self-renewal capability and ability to differentiate into various cell types of the bronchial epithelium are promising for developing a long-term and effective therapy. Regarding bronchial erosion, we found that promoting cell engraftment is crucial due to the barrier function of the intact bronchial epithelium and the lack of selective advantage of corrected cells. Various chemical and enzymatic strategies have shown potential, but their safety for in-vivo use needs further assessment. Furthermore, GFP-expressing engrafted cells displaying cilia suggest successful differentiation into ciliated cells, though functional recovery still requires confirmation.</div><div>In conclusion, the engraftment of corrected lung progenitors into eroded bronchial epithelium appears to be a promising therapeutic strategy to PCD. Next step of the project involves developing this therapy for in-vivo application, assessing its safety and efficacy in an immunodeficient mini-pig model.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 194-195"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}