Revue des maladies respiratoires最新文献

{"title":"Mise en place d’un modèle de fibrose pulmonaire murin et porcin et tests d’inhibition génique","authors":"K. Tazibet , V. Gouyer , L. Vandomber , C. Chenivesse , J.-L. Desseyn","doi":"10.1016/j.rmr.2025.12.047","DOIUrl":"10.1016/j.rmr.2025.12.047","url":null,"abstract":"<div><h3>Introduction</h3><div>La fibrose pulmonaire idiopathique (FPI) est une maladie pulmonaire rare, grave et évolutive, caractérisée par une fibrose progressive et irréversible. Les traitements antifibrosants ralentissent, sans stopper le déclin de la fonction respiratoire. Les modèles expérimentaux ont des limites ; il est nécessaire de développer de nouvelles approches pour évaluer de potentielles cibles thérapeutiques. La fibrose pulmonaire ex vivo, induite par un cocktail fibrosant (CF) sur des <em>precision-cut lung slices</em> (PCLS), reproduit plusieurs aspects cellulaires de la FPI <span><span>[1]</span></span>. Dans un modèle d’explants pulmonaires embryonnaires murins (EPEM) <span><span>[2]</span></span>, les gènes <em>lipocalin-2 (Lcn2)</em>, <em>serum amyloid protein 3 (Saa3)</em> et <em>serpin familyÀ member 3a (Serpina3a)</em> ont été identifiés comme précocement surexprimés après exposition au CF avant que la fibrose n’apparaisse sur le plan histologique. Ces gènes présentent un intérêt biologique potentiel en tant que cibles thérapeutiques. L’objectif de ce travail est de développer un modèle adulte de fibrose pulmonaire ex vivo sur poumons de souris et de porc, identifier les gènes précocement surexprimés et tester leur inhibition par oligonucléotides antisens (OAS).</div></div><div><h3>Méthodes</h3><div>Des PCLS ont été préparés à partir de poumons entiers de souris de type sauvage (C57BL/6) et de punchs de poumons de porc d’épaisseur 250 et 400 micromètres respectivement. À 24<!--> <!-->h de culture, ils ont été exposés quotidiennement à un CF associant cytokines et agents irritants pendant 5<!--> <!-->jours. La fibrose a été évaluée par le score d’Ashcroft modifié sur des coupes colorées au Trichrome de Masson et l’expression de gènes pro-fibrosants par RT-qPCR TaqMan (<em>Tgf-β1, Acta-2, Col1a1</em>). Les gènes précocement surexprimés dans le modèle EPEM ont été recherchés par RT-qPCR TaqMan à 16<!--> <!-->h de traitement. Les tissus traités ont ensuite été exposés à des OAS (2<!--> <!-->μM) ciblant les gènes surexprimés. Les comparaisons statistiques ont utilisé des tests non paramétriques.</div></div><div><h3>Résultats</h3><div>Les PCLS traités ont des scores de fibrose significativement plus élevés chez le porc (<em>n</em> <!-->=<!--> <!-->29 paires PCLS traités/non traités) (<span><span>Figure 1</span></span>) et la souris (<em>n</em> <!-->=<!--> <!-->17 paires PCLS traités/non traités) par rapport aux PCLS non traités. Le gène <em>Tgf-β1</em> est surexprimé par les PCLS murins traités. À 16<!--> <!-->h de traitement, <em>Lcn2</em> (<em>n</em> <!-->=<!--> <!-->11 paires PCLS traités/non traités) et <em>Saa3</em> (<em>n</em> <!-->=<!--> <!-->6 paires PCLS traités/non traités) sont surexprimés (×2,6 et ×4,3 respectivement) par les PCLS murins, alors qu’aucune différence n’est retrouvée pour <em>Serpina3a</em> (<em>n</em> <!-->=<!--> <!-->9 paires PCLS traités/non traités). L’expression de ces gènes n’est pas détectée p","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Pages 25-26"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855243","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":"Amphiregulin reflects brain metastasis progression and leads to PD-L1 expression in non-small cell lung cancer cells","authors":"D. Leite Ferreira ,&nbsp;T. Biojout ,&nbsp;C. Bazille ,&nbsp;M. Guyot ,&nbsp;L. Malandain ,&nbsp;L. Charrier ,&nbsp;J. Toutain ,&nbsp;E. Peres ,&nbsp;S. Valable ,&nbsp;J. Madelaine ,&nbsp;J. Levallet ,&nbsp;G. Levallet ,&nbsp;E. Bergot","doi":"10.1016/j.rmr.2025.12.005","DOIUrl":"10.1016/j.rmr.2025.12.005","url":null,"abstract":"<div><h3>Introduction</h3><div>The Hippo kinase Nuclear Dbf2-related kinase 2 (NDR2) promotes brain metastasis (BM) in non-small cell lung cancer (NSCLC) by disrupting Yes-associated protein 1 (YAP-1), suggesting a role in circulating tumor cells and/or brain colonization. However, the underlying mechanism remains to be clarified.</div></div><div><h3>Methods</h3><div>Human bronchial epithelial tumor cells (HBECs)–A549, H₁₉₇₅, H₂₀₃₀, and the brain-tropic H₂₀₃₀-BrM3 line–depleted or not of NDR2 (via siRNA or shRNA), were exposed to shear stress (up to 40<!--> <!-->dyn/cm² for 3<!--> <!-->hours) using an Ibidi® pump system, in the presence or absence of exogenous Amphiregulin (AREG), and subsequently reseeded or not. Viability, apoptosis, proliferation, and YAP-dependent gene expression were analyzed. H₂₀₃₀-BrM3 cells (shControl or shNDR2) were injected intracardially into nude athymic mice (<em>n</em> <!-->=<!--> <!-->10/group) to evaluate plasma AREG levels correlation with BM. AREG expression was assessed in human NSCLC tumor samples from primary and/or brain metastatic sites.</div></div><div><h3>Results</h3><div>HBECs tolerated shear stress and showed reduced apoptosis after reseeding when expressing NDR2. Shear stress induced a stem-like phenotype (via Sox2/9 variation) and increased AREG expression in most HBECs. AREG enhanced HBEC survival and proliferation under shear stress. In mice, plasma AREG levels correlated with BM volume. In human NSCLC samples, AREG positive tumors displayed elevated Programmed Death-Ligand 1 (PD-L1), suggesting immune escape. Exogenous AREG treatment in H₂₀₃₀-BrM3 cells induced PD-L1 expression in vitro.</div></div><div><h3>Conclusion</h3><div>AREG supports tumor adaptation to mechanical stress and may drive immune tolerance via PD-L1. Its correlation with BM burden highlights its potential as a biomarker and therapeutic target in NSCLC.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Page 4"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855302","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":"Exploring COPD using a complex tubular model of distal airways integrating epithelial and mesenchymal compartments","authors":"K. Raasch ,&nbsp;E. Latouille ,&nbsp;E. Maurat ,&nbsp;A. Richard ,&nbsp;P. Henrot ,&nbsp;M. Zysman ,&nbsp;V. Bergeron ,&nbsp;P. Esteves ,&nbsp;M. Thumerel ,&nbsp;H. Bégueret ,&nbsp;P. Nassoy ,&nbsp;P. Berger ,&nbsp;G. Recher ,&nbsp;L. Andrique ,&nbsp;I. Dupin","doi":"10.1016/j.rmr.2025.12.017","DOIUrl":"10.1016/j.rmr.2025.12.017","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory disease characterized by a progressive decline of lung function. The limitation of expiratory airflow primarily affects distal airways, which show early signs of remodelling, inflammation and obliteration. The limited relevance of 2D cell models and lack of 3D models mimicking small airway features hinder early pathophysiological understanding and drug discovery. We have previously developed a 3D mesenchyme-free tubular “bronchioid” model.</div></div><div><h3>Methods</h3><div>Here, we aimed to incorporate bronchial smooth muscle (BSM) cells within the bronchioid model to investigate epithelial-mesenchymal interactions in COPD. We used a tubuloid cell-based assay and human bronchial epithelial and smooth mucle cells derived from clinical samples.</div></div><div><h3>Results</h3><div>Spatially control of dual cell encapsulation was required to obtain a tubular epithelial structure surrounded by a peripheral concentric layer of BSM cells, mimicking bronchial topology. Adding the BSM cell population improved the robustness of the system. BSM cells exhibit active proliferation during the first two weeks before becoming largely quiescent, whereas BECs continue to proliferate throughout the culture period. We observed a greater persistence of basal epithelial cells in the bi-compartment bronchioid compared to the mesenchyme-free model, along with a shift toward more secretory cells. Calcium imaging following carbachol stimulation confirmed the ability of BSM cells to respond to a cholinergic stimulus. Bronchoconstriction and release, differentiation level and regeneration properties will be next tested in COPD and non-COPD-derived bronchioids.</div></div><div><h3>Conclusion</h3><div>We conclude that the bi-component bronchioid enables modeling of the distal lung's epithelial-mesenchymal unit and serves as a powerful tool for understanding COPD pathogenesis.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Page 11"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855304","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":"Validité métrologique de deux oxymètres alternatifs pour la mesure de la SpO2","authors":"J. Frija ,&nbsp;L. Abensur-Vuillaume ,&nbsp;F. Kerzabi ,&nbsp;M. Grajoszex ,&nbsp;M.-P. d’Ortho","doi":"10.1016/j.rmr.2025.12.060","DOIUrl":"10.1016/j.rmr.2025.12.060","url":null,"abstract":"","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Pages 109-111"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041569","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":"Voyage en Afrique du Sud d’une patiente sous anti-TNF : la tuberculose était-elle évitable ?","authors":"A. Gerard ,&nbsp;S. Manni ,&nbsp;K. Risso ,&nbsp;D. Viard ,&nbsp;M. Vassallo ,&nbsp;F. Vandenbos","doi":"10.1016/j.rmr.2025.12.002","DOIUrl":"10.1016/j.rmr.2025.12.002","url":null,"abstract":"<div><h3>Introduction</h3><div>La tuberculose maladie (TM) est toujours redoutée chez les patients traités par anti-TNF. C’est pourquoi le dépistage de l’infection tuberculeuse latente (ITL) doit être réalisé avant le début du traitement. L’éducation thérapeutique du patient doit ensuite permettre de limiter le risque de contamination sous traitement.</div></div><div><h3>Observation</h3><div>Nous rapportons le cas d’une patiente de 19 ans hospitalisée pour une tuberculose disséminée. Elle était traitée depuis 2 ans par de l’adalimumab pour une maladie de Crohn. La mise en place du traitement par anti-TNF avait été précédée d’un dépistage négatif pour une ITL. La patiente a développé, trois mois après le retour d’un voyage d’études de 4 mois en Afrique du Sud, une tuberculose disséminée qui a nécessité plusieurs hospitalisations. L’atteinte était pulmonaire, ganglionnaire étagée, oculaire et splénique. Le traitement antituberculeux a consisté en une quadrithérapie pendant 2 mois, suivie d’une bithérapie pendant 10 autres mois. La patiente en a gardé quelques séquelles radiologiques.</div></div><div><h3>Conclusion</h3><div>Un voyage dans un pays de forte endémie de la tuberculose est un facteur de risque de TM chez les patients sous anti-TNF. Le choix d’une prophylaxie aurait pu être discuté.</div></div><div><h3>Introduction</h3><div>Active tuberculosis disease (ATB) remains feared in patients treated with TNF inhibitors. For that reason, screening for latent tuberculosis infection (LTBI) is currently performed before the start of treatment. Therapeutic patient education (TPE) should consequently help reduce the risk of infection during treatment.</div></div><div><h3>Observation</h3><div>We report the case of a 19-year-old female patient hospitalized for disseminated tuberculosis. She had been treated for two years with adalimumab for Crohn's disease. Screening for LTBI had been performed before the initiation of anti-TNF treatment and was negative. Three months after returning from a four-month study trip to South Africa, the patient nevertheless developed disseminated tuberculosis and was repeatedly hospitalized. The disease was at once pulmonary, lymphatic, ocular, and splenic. Antituberculosis treatment consisted of quadruple therapy for two months followed by dual therapy for an additional 10 months. The patient was disabled for one year and suffered some radiological sequelae.</div></div><div><h3>Conclusion</h3><div>Traveling to a country with high tuberculosis endemicity is a risk factor for ATB in patients undergoing anti-TNF therapy. Antibioprophylaxis may have been considered prior to the trip.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Pages 96-99"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782558","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":"Effects of second hand cigarette smoke exposure on alveolarization in C57Bl/6J mice pups","authors":"T. De Freitas Castro ,&nbsp;M. Toigo ,&nbsp;A. Boiret ,&nbsp;J. Campo ,&nbsp;P. Abou Atmeh ,&nbsp;L. Boyer ,&nbsp;E. Zana-Taïeb","doi":"10.1016/j.rmr.2025.12.048","DOIUrl":"10.1016/j.rmr.2025.12.048","url":null,"abstract":"<div><h3>Introduction</h3><div>Smoking during pregnancy is a significant risk factor for intrauterine growth restriction and respiratory diseases. However, mechanisms involved in this process are not well defined.</div></div><div><h3>Objective</h3><div>The objective are to evaluate the effects of prenatal tobacco exposure on early postnatal lung development.</div></div><div><h3>Methods</h3><div>Mice were randomly divided into two groups: control (CTL) or second hand tobacco exposure (CS) group starting 5 days before mating and during gestation. Lung morphometry, immunofluorescence (IF), and 3D positive EPCAM+ cells culture were performed at 10 and 21 days of postnatal life (P10 and P21). IF markers were SpC+ for AT2, Krt8 for pre-alveolar differentiate intermediate cell (pre-ADI) and Ki67 for cell proliferation.</div></div><div><h3>Results</h3><div>Weight, height and Lee index were lower in CS compared to CTL group. Morphometric study showed an increase of mean linear intercept in CS animals at P10 (<em>p</em> <!-->&lt;<!--> <!-->0.05) without any differences at P21. IF analysis showed a decrease of AT2 cells (SpC+/Dapi) in the CS group compared with CTL at P21. Proliferation of AT2 (Spc+/Ki67<!--> <!-->+<!--> <!-->) were significantly increased in CS group compared to control at P10 and P21. Number of pre-ADI cells (Spc+/Krt8<!--> <!-->+<!--> <!-->) was significantly increased in CS group at P10 but not at P21. Alveolospheres analysis showed a significant increase of Epcam+ cells number in CS group at P10 compared to control (<em>P</em> <!-->&lt;<!--> <!-->0.05).</div></div><div><h3>Conclusion</h3><div>Antenatal CS exposure disturbs growth and early lung development. Higher proliferation of Epcam+ cells at P10 and increased differentiation allows an alveolarization catch-up on P21. Further studies are needed to better characterize the alveolar niche after antenatal CS exposure.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Page 26"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147854684","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":"An artificial intelligence-based model exploiting H&E images to assess the response of airway submucosal glands to cigarette smoke","authors":"E. Maurat ,&nbsp;O. Saut ,&nbsp;H. Bégueret ,&nbsp;M. Thumerel ,&nbsp;M. Zysman ,&nbsp;P. Brochart ,&nbsp;F. Delva ,&nbsp;I. Dupin","doi":"10.1016/j.rmr.2025.12.023","DOIUrl":"10.1016/j.rmr.2025.12.023","url":null,"abstract":"<div><h3>Background</h3><div>Cigarette smoke is a major global health concern due to its detrimental effects on the respiratory system. The respiratory tract is directly exposed to harmful particles and chemicals present in tobacco smoke. We hypothesize that lung resilience depends on the airway submucosal gland (SMG), an ectodermal appendage lining the airways, renowned for its unique properties in mucus secretion, antimicrobial activity and a potential niche for proximal airway stem cells. The objective of this study is to assess the relationship between SMG size and structure and cigarette smoke exposure, using an artificial intelligence (AI)-based approach. The analysis is based on hematoxylin and eosin (H&amp; E)-stained sections from 278 non-diseased bronchial specimens, sampled from non-diseased regions and obtained from the “CaProMat” cohort, which includes lung cancer patients with characterized occupational and tobacco smoke exposure.</div></div><div><h3>Methods</h3><div>We developed a supervised AI-based approach to automatically segment SMG ducts and acini, airway epithelium, bronchial smooth muscle and cartilage structures from H&amp; E-stained slides. The model was trained on a dataset of 29 annotated images. Performance evaluation showed promising results, with all target structures achieving mean Dice similarity coefficients exceeding 0.8.</div></div><div><h3>Result and conclusion</h3><div>AI-powered analysis of H&amp; E-stained sections is a promising tool for identifying tissue-relevant features and exploring the relationship between spatial tissue patterns and particulate exposure. Our preliminary findings show that SMG area is larger in former smokers compared to non-smokers, with a further increase observed in active smokers. These results suggest that SMGs undergo adaptive changes in response to particulate exposure, which may be partially reversible after exposure cessation.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Pages 13-14"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855051","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":"Integrating Single-Cell RNA sequencing analysis to assess functional plasticity alterations of airway epithelial cells during sepsis","authors":"A. Azmoudeh ,&nbsp;B. Saint-Pierre ,&nbsp;F. Pène ,&nbsp;M.-Z. Ladjemi","doi":"10.1016/j.rmr.2025.12.031","DOIUrl":"10.1016/j.rmr.2025.12.031","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, often leading to organ dysfunction. While &gt;85% of patients now survive the primary episode due to advances in treatment, they remain highly susceptible to ICU-acquired pneumonia. The airway epithelium, a key regulator of lung immune responses, may undergo sepsis-induced alterations that impair anti-infective defense.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We analyzed publicly available single-cell RNA sequencing data set (GSE207651) from a murine model of extra-pulmonary polymicrobial sepsis to investigate epithelial cell-specific transcriptional alterations during sepsis. Bioinformatic analyses were performed in R using &lt;em&gt;Seurat&lt;/em&gt; for data preprocessing, integration, and clustering and &lt;em&gt;clusterProfiler&lt;/em&gt; (enrichGO function) for functional enrichment analysis based on Gene Ontology Biological Processes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;ScRNA-seq analysis of lung tissues obtained 24&lt;!--&gt; &lt;!--&gt;h and 48&lt;!--&gt; &lt;!--&gt;h after Ceacal ligation and puncture (CLP) or sham-operated mice revealed epithelial cell type–specific transcriptomic alterations. Alveolar Type I cells (AT I) showed no transcriptional changes. In contrast, ciliated, club, and alveolar type II (AT II) cells exhibited upregulation of &lt;em&gt;S100a8&lt;/em&gt; and &lt;em&gt;S100a9&lt;/em&gt;, consistent with enhanced inflammatory signaling post-sepsis. Club cells showed increased expression of &lt;em&gt;Fmo2&lt;/em&gt;, &lt;em&gt;Pdk4&lt;/em&gt;, and &lt;em&gt;Cyp2b10&lt;/em&gt;, indicating altered fatty acid metabolism and oxidation. Both ciliated and AT II cells exhibited downregulation of genes involved in chaperone-mediated protein folding (e.g. &lt;em&gt;Hsp8&lt;/em&gt;, &lt;em&gt;Hsp90ab1&lt;/em&gt;, &lt;em&gt;St13&lt;/em&gt;) and upregulation of &lt;em&gt;Lcn2&lt;/em&gt; (ROS biosynthesis). Specifically in ciliated cells, we observed downregulation of cellular respiration and mitochondrial organization related genes (e.g. &lt;em&gt;Cox8a&lt;/em&gt;, &lt;em&gt;Cox17&lt;/em&gt; and &lt;em&gt;Hmgb1&lt;/em&gt;), and of the &lt;em&gt;Ptn&lt;/em&gt; gene, which encodes pleiotrophin, suggesting an impaired epithelial repair process. Additionally, ciliated cells showed reduced expression of genes associated with microtubule and ciliary movement (e.g. &lt;em&gt;Dnaj1&lt;/em&gt;, &lt;em&gt;Tubb4b&lt;/em&gt;, and &lt;em&gt;Tuba1a&lt;/em&gt;). AT II-specific changes included increased expression of &lt;em&gt;Slpi&lt;/em&gt; (inhibition of serine proteases such as neutrophil elastase), and &lt;em&gt;Rgcc&lt;/em&gt;, &lt;em&gt;Ngp&lt;/em&gt;, &lt;em&gt;Foxp1&lt;/em&gt; (endothelial proliferation/VEGF regulation) and reduced &lt;em&gt;Cd36&lt;/em&gt;, &lt;em&gt;Slc12a2&lt;/em&gt; (wound healing), &lt;em&gt;Scgb1a1&lt;/em&gt; (immune modulation and epithelial repair), surfactant genes (&lt;em&gt;Sftpc&lt;/em&gt;, &lt;em&gt;Sftpa&lt;/em&gt;) and &lt;em&gt;Cldn18&lt;/em&gt; (barrier integrity).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Together, these findings indicate that sepsis induces a profound and cell type–specific transcriptional reprogramming of respiratory epithelial cells potentially contributing to impaired inflammatory response, cellular respiration and en","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Pages 17-18"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855053","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":"Role of CD146 in bronchial epithelial differentiation and repair: implications for severe asthma","authors":"F. Lepretre ,&nbsp;L. Moreno ,&nbsp;K. Valette ,&nbsp;A. Joshkon ,&nbsp;N. Bardin ,&nbsp;M. Blot-Chabaud ,&nbsp;P. Chanez ,&nbsp;D. Gras","doi":"10.1016/j.rmr.2025.12.014","DOIUrl":"10.1016/j.rmr.2025.12.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Asthma is a chronic respiratory disease affecting nearly 300 million people worldwide, with 2–10% suffering from severe asthma. Bronchial epithelium dysfunction plays a central role in asthma pathophysiology. CD₁₄₆, an adhesion molecule highly expressed in vascular cells, is also present in epithelial cells, although its functions in this context remain poorly understood. We previously reported that CD₁₄₆ is expressed by the bronchial epithelium and mainly by the basal cells. This study aimed to investigate the role of CD₁₄₆ in bronchial epithelium differentiation and repair, and its implication in severe asthma.</div></div><div><h3>Methods</h3><div>Bronchial epithelia from healthy controls (C) and severe asthma (SA) patients were reconstituted in vitro using air-liquid interface culture. Undifferentiated bronchial epithelial cells (<em>n</em> <!-->=<!--> <!-->10<!--> <!-->C; 6 SA) and CD₁₄₆₋ sorted cells (<em>n</em> <!-->=<!--> <!-->10<!--> <!-->C; 5 SA) were followed during differentiation. In parallel, CD₁₄₆ expression was further assessed in differentiated epithelia (<em>n</em> <!-->=<!--> <!-->30<!--> <!-->C; 26 SA). Then, CD₁₄₆ was silenced using lentiviral shRNA in undifferentiated bronchial epithelial cells and its effects were followed until obtention of a fully differentiated epithelium (<em>n</em> <!-->=<!--> <!-->2). Finally, to better understand the potential involvement of CD₁₄₆ in repair process, CD₁₄₆ expression kinetics were evaluated in a 14-day virus-induced exacerbation model (<em>n</em> <!-->=<!--> <!-->6<!--> <!-->C; 6 SA).</div></div><div><h3>Results</h3><div>Loss of CD₁₄₆ impaired epithelial differentiation, as evidenced by poorly differentiated epithelia reconstituted from CD₁₄₆₋ cells. In unsorted cultures, CD₁₄₆ expression decreased during differentiation (−70% from day 0 to day 28, <em>p</em> <!-->&lt;<!--> <!-->0.05), while shRNA-mediated silencing seems to confirm its role in this process. In severe asthma, CD₁₄₆ was significantly overexpressed at both mRNA (+219%, p&lt; 0.0001) and protein (+34%, <em>p</em> <!-->&lt;<!--> <!-->0.05) levels in differentiated epithelium and differences in the differentiation has been observed. During a virus-induced exacerbation, CD₁₄₆ seems to be involved in the epithelium repair.</div></div><div><h3>Conclusion</h3><div>Our findings identify CD₁₄₆ as a key regulator of bronchial epithelial differentiation and repair. Its overexpression in severe asthma highlights a potential contribution to disease pathophysiology and suggests CD₁₄₆ as a novel target for therapeutic investigation.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Page 9"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855057","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":"Evaluating the immune checkpoint TIGIT as a novel target in pulmonary fibrosis","authors":"A.-V. Curioni ,&nbsp;D. Pokhreal ,&nbsp;X. Li ,&nbsp;P. Le Guen ,&nbsp;Y. Cartier ,&nbsp;P. De La Rochère ,&nbsp;F. Sônego ,&nbsp;B. Crestani ,&nbsp;G.-D. Helou","doi":"10.1016/j.rmr.2025.12.044","DOIUrl":"10.1016/j.rmr.2025.12.044","url":null,"abstract":"<div><h3>Introduction</h3><div>Idiopathic pulmonary fibrosis (IPF) represents the most frequent and severe type of lung fibrosis, with limited therapeutic options <span><span>[1]</span></span>. While the immune system's role in IPF remains debated, its contribution via the production of key fibrotic mediators is established. In particular, regulatory T cells (Tregs) secrete transforming growth factor beta (TGF-β) and interleukin (IL-) 10, promoting the proliferation of fibroblasts. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an immune checkpoint implicated in different pathological contexts, notably cancer. High TIGIT expression marks enhanced Tregs’ suppressive functions, associated with fibrinogen-like protein 2 and IL-10 production upon ligation <span><span>[2]</span></span>. Building on this, we aimed to characterize TIGIT expression in the lungs of IPF patients and to assess the impact of its inhibition on lung fibrosis progression.</div></div><div><h3>Methods</h3><div>Transcriptomic data from the IPF atlas were reanalysed to characterize TIGIT gene expression in lung immune cells. TIGIT levels were also quantified in bronchoalveolar lavage fluid (BAL) cells and correlated with disease severity. Pulmonary fibrosis was induced in FoxP3-GFP and humanized TIGIT (hTIGIT) knock-in mice. Lungs and BAL were collected 7 or 14 days (D) after intranasal exposure to bleomycin (BLM), and immunophenotyping was performed using flow cytometry. hTIGIT mice were injected at D₈and D₁₁with a human TIGIT antagonist “Tiragolumab” or an isotype control, and lung fibrosis was assessed.</div></div><div><h3>Results</h3><div>TIGIT is most highly expressed by Tregs in the lungs and is significantly upregulated in IPF relative to healthy donors. The percentage of TIGIT+ Tregs is elevated in the BAL of IPF patients, but no correlation is revealed with respiratory function, sex, or smoking status. In both mouse models, Treg count increases upon BLM stimulation, and the percentage of TIGIT+ Tregs is significantly enhanced during the fibrotic phase (D₁₄). Interestingly, TIGIT+ cells display an upregulated expression of FoxP3 and CD₂₅as compared to TIGIT- cells, and an increased secretion of IL-13 and IL-10 in lungs at D₁₄. Treatment of hTIGIT mice with Tiragolumab does not affect the development of lung fibrosis. Specifically, no changes were observed in body weight, collagen production, or in the number and activation status of pulmonary myeloid and lymphoid cells.</div></div><div><h3>Conclusion</h3><div>TIGIT emerges as a promising marker of pulmonary Treg fibrotic activity in IPF, however, treatment of humanized mice with Tiragolumab does not affect lung fibrosis progression under our experimental conditions. More studies are needed to evaluate the effects of other TIGIT modulators on the fibrotic activity of immune cells, both in preclinical mouse models and in primary human lung cells.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"43 1","pages":"Page 24"},"PeriodicalIF":0.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855059","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}