Mucosal Immunology最新文献_第8页

Migratory CD103+CD11b+ cDC2s in Peyer’s patches are critical for gut IgA responses following oral immunization 佩尔斑块中的迁移性 CD103+CD11b+ cDC2 细胞对口服免疫后的肠道 IgA 反应至关重要。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-08-01 DOI: 10.1016/j.mucimm.2024.03.004

{"title":"Migratory CD103+CD11b+ cDC2s in Peyer’s patches are critical for gut IgA responses following oral immunization","authors":"","doi":"10.1016/j.mucimm.2024.03.004","DOIUrl":"10.1016/j.mucimm.2024.03.004","url":null,"abstract":"<div>Induction and regulation of specific intestinal immunoglobulin (Ig)A responses critically depend on dendritic cell (DC) subsets and the T cells they activate in the Peyer’s patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of cluster of differentiation (CD)103− conventional DC (cDC)2s and lysozyme-expressing DC (LysoDCs) in the subepithelial dome and of CD103+ cDC2s that expressed CD101 in the T cell zones, while oral ovalbumin (OVA) tolerization was instead associated with greater accumulation of cDC1s and peripherally induced regulatory T cells (pTregs) in this area. Decreased IgA responses were observed after CT-adjuvanted immunization in huCD207DTA mice lacking CD103+ cDC2s, while oral OVA tolerization was inefficient in cDC1-deficient Batf3−/− mice. Using OVA transgenic T cell receptor CD4 T cell adoptive transfer models, we found that co-transferred endogenous wildtype CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of interleukin-10. CT could overcome this blocking effect, apparently through a modulating effect on pTregs while promoting an expansion of follicular helper T cells. The data support a model where cDC1-induced pTreg normally suppresses PP responses for any given antigen and where CT’s oral adjuvanticity effect is dependent on promoting follicular helper T cell responses through induction of CD103+ cDC2s.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 509-523"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000230/pdfft?md5=42319928de33273b0707e29512332b31&pid=1-s2.0-S1933021924000230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-5 antagonism reverses priming and activation of eosinophils in severe eosinophilic asthma IL-5 拮抗剂可逆转严重嗜酸性粒细胞性哮喘中嗜酸性粒细胞的引诱和激活。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-08-01 DOI: 10.1016/j.mucimm.2024.03.005

{"title":"IL-5 antagonism reverses priming and activation of eosinophils in severe eosinophilic asthma","authors":"","doi":"10.1016/j.mucimm.2024.03.005","DOIUrl":"10.1016/j.mucimm.2024.03.005","url":null,"abstract":"<div>Eosinophils are key effector cells mediating airway inflammation and exacerbation in patients with severe eosinophilic asthma. They are present in increased numbers and activation states in the airway mucosa and lumen. Interleukin-5 (IL-5) is the key eosinophil growth factor that is thought to play a role in eosinophil priming and activation. However, the mechanism of these effects is still not fully understood. The anti-IL-5 antibody mepolizumab reduces eosinophil counts in the airway modestly but has a large beneficial effect on the frequency of exacerbations of severe eosinophilic asthma, suggesting that reduction in eosinophil priming and activation is of central mechanistic importance. In this study, we used the therapeutic effect of mepolizumab and single-cell ribonucleic acid sequencing to investigate the mechanism of eosinophil priming and activation by IL-5. We demonstrated that IL-5 is a dominant driver of eosinophil priming and plays multifaceted roles in eosinophil function. It enhances eosinophil responses to other stimulators of migration, survival, and activation by activating phosphatidylinositol-3-kinases, extracellular signal-regulated kinases, and p38 mitogen-activated protein kinases signaling pathways. It also enhances the pro-fibrotic roles of eosinophils in airway remodeling via transforming growth factor-β pathway. These findings provide a mechanistic understanding of eosinophil priming in severe eosinophilic asthma and the therapeutic effect of anti-IL-5 approaches in the disease.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 524-536"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000242/pdfft?md5=c3cb4d4c96ef77859fa4efa2e7e63cdf&pid=1-s2.0-S1933021924000242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells 舌下过敏原免疫疗法通过树突状细胞介导的 Foxp3+ 调节性 T 细胞诱导防止屋尘螨吸入性 2 型免疫

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-08-01 DOI: 10.1016/j.mucimm.2024.03.012

{"title":"Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells","authors":"","doi":"10.1016/j.mucimm.2024.03.012","DOIUrl":"10.1016/j.mucimm.2024.03.012","url":null,"abstract":"<div>Sublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma and a potential disease-modifying strategy for asthma prevention. The key cellular events leading to such long-term tolerance remain to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM)-driven allergic asthma. HDM extract was sublingually administered over 3 weeks followed by intratracheal sensitization and intranasal challenges with HDM. Prophylactic SLIT prevented allergic airway inflammation and hyperreactivity with a low lab-to-lab variation. The HDM-specific T helper (Th)2 (cluster of differentiation 4 Th) response was shifted by SLIT toward a regulatory and Th17 response in the lung and mediastinal lymph node. By using Derp1-specific cluster of differentiation 4+ T cells (1-DER), we found that SLIT blocked 1-DER T cell recruitment to the mediastinal lymph node and dampened IL-4 secretion following intratracheal HDM sensitization. Sublingually administered Derp1 protein activated 1-DER T cells in the cervical lymph node via chemokine receptor7+ migratory dendritic cells (DC). DCs migrating from the oral submucosa to the cervical lymph node after SLIT-induced Foxp3+ regulatory T cells. When mice were sensitized with HDM, prior prophylactic SLIT increased Derp1 specific regulatory T cells (Tregs) and lowered Th2 recruitment in the lung. By using Foxp3-diphtheria toxin receptor mice, Tregs were found to contribute to the immunoregulatory prophylactic effect of SLIT on type 2 immunity. These findings in a mouse model suggest that DC-mediated functional Treg induction in oral mucosa draining lymph nodes is one of the driving mechanisms behind the disease-modifying effect of prophylactic SLIT.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 618-632"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193302192400028X/pdfft?md5=e2fdf11008693b629cfefb85e653971d&pid=1-s2.0-S193302192400028X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140585059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nur77 as a novel regulator of Paneth cell differentiation and function Nur77是Paneth细胞分化和功能的新型调节因子

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-08-01 DOI: 10.1016/j.mucimm.2023.09.001

{"title":"Nur77 as a novel regulator of Paneth cell differentiation and function","authors":"","doi":"10.1016/j.mucimm.2023.09.001","DOIUrl":"10.1016/j.mucimm.2023.09.001","url":null,"abstract":"<div>Serving as a part of intestinal innate immunity, Paneth cells play an important role in intestinal homeostasis maintenance via their multiple functions. However, the regulation of Paneth cells has been proven to be complex and diverse. Here, we identified nuclear receptor Nur77 as a novel regulator of Paneth cell differentiation and function. Nur77 deficiency led to the loss of Paneth cells in murine ileal crypts. Intestinal tissues or organoids with Nur77 deficiency exhibited the impaired intestinal stem cell niche and failed to enhance antimicrobial peptide expression after Paneth cell degranulation. The defects in Paneth cells and antimicrobial peptides in Nur7−/− mice led to intestinal microbiota disorders. Nur77 deficiency rendered postnatal mice susceptible to necrotizing enterocolitis. Mechanistically, Nur77 transcriptionally inhibited Dact1 expression to activate Wnt signaling activity, thus promoting Paneth cell differentiation and function. Taken together, our data suggest the regulatory role of Nur77 in Paneth cell differentiation and function and reveal a novel Dact1-mediated Wnt inhibition mechanism in Paneth cell development.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 752-767"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000673/pdfft?md5=03b6c52ad22113693dccb24cbfdb2729&pid=1-s2.0-S1933021923000673-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells 人类整个生命周期的小肠单细胞图谱显示了胎儿免疫细胞的独特特征。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-08-01 DOI: 10.1016/j.mucimm.2024.03.011

{"title":"Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells","authors":"","doi":"10.1016/j.mucimm.2024.03.011","DOIUrl":"10.1016/j.mucimm.2024.03.011","url":null,"abstract":"<div>Proper development of mucosal immunity is critical for human health. Over the past decade, it has become evident that in humans, this process begins in utero. However, there are limited data on the unique features and functions of fetal mucosal immune cells. To address this gap, we integrated several single-cell ribonucleic acid sequencing datasets of the human small intestine (SI) to create an SI transcriptional atlas throughout the human life span, ranging from the first trimester to adulthood, with a focus on immune cells. Fetal SI displayed a complex immune landscape comprising innate and adaptive immune cells that exhibited distinct transcriptional programs from postnatal samples, especially compared with pediatric and adult samples. We identified shifts in myeloid populations across gestation and progression of memory T-cell states throughout the human lifespan. In particular, there was a marked shift of memory T cells from those with stem-like properties in the fetal samples to fully differentiated cells with a high expression of activation and effector function genes in adult samples, with neonatal samples containing both features. Finally, we demonstrate that the SI developmental atlas can be used to elucidate improper trajectories linked to mucosal diseases by implicating developmental abnormalities underlying necrotizing enterocolitis, a severe intestinal complication of prematurity. Collectively, our data provide valuable resources and important insights into intestinal immunity that will facilitate regenerative medicine and disease understanding.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 599-617"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193302192400031X/pdfft?md5=cfc78089a5ac44e4ae42a7991fde8b5d&pid=1-s2.0-S193302192400031X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Local complement activation and modulation in mucosal immunity 粘膜免疫中的局部补体激活和调节。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-08-01 DOI: 10.1016/j.mucimm.2024.05.006

引用次数: 0

The bacterial lysate OM-85 engages Toll-like receptors 2 and 4 triggering an immunomodulatory gene signature in human myeloid cells 细菌裂解物 OM-85 与 Toll 样受体 2 和 4 结合，触发人类髓系细胞的免疫调节基因特征。

IF 8 2区医学

Mucosal Immunology Pub Date : 2024-06-01 DOI: 10.1016/j.mucimm.2024.02.010

Hanif J. Khameneh , Marco Bolis , Pedro M.O. Ventura , Giada A. Cassanmagnago , Berenice A. Fischer , Alessandro Zenobi , Jessica Guerra , Irene Buzzago , Maurizio Bernasconi , Guido J.R. Zaman , Andrea Rinaldi , Simone G. Moro , Federica Sallusto , Edouard Baulier , Christian Pasquali , Greta Guarda

{"title":"The bacterial lysate OM-85 engages Toll-like receptors 2 and 4 triggering an immunomodulatory gene signature in human myeloid cells","authors":"Hanif J. Khameneh , Marco Bolis , Pedro M.O. Ventura , Giada A. Cassanmagnago , Berenice A. Fischer , Alessandro Zenobi , Jessica Guerra , Irene Buzzago , Maurizio Bernasconi , Guido J.R. Zaman , Andrea Rinaldi , Simone G. Moro , Federica Sallusto , Edouard Baulier , Christian Pasquali , Greta Guarda","doi":"10.1016/j.mucimm.2024.02.010","DOIUrl":"10.1016/j.mucimm.2024.02.010","url":null,"abstract":"<div>OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed. Here, we show that the immune response to OM-85 in the mouse is largely mediated by myeloid immune cells through Toll-like receptor (TLR) 4 in vitro and in vivo. Instead, in human immune cells, TLR2 and TLR4 orchestrate the response to OM-85, which binds to both receptors as shown by surface plasmon resonance assay. Ribonucleic acid-sequencing analyses of human monocyte-derived dendritic cells reveal that OM-85 triggers a pro-inflammatory signature and a unique gene set, which is not induced by canonical agonists of TLR2 or TLR4 and comprises tolerogenic genes. A largely overlapping TLR2/4-dependent gene signature was observed in individual subsets of primary human airway myeloid cells, highlighting the robust effects of OM-85. Collectively, our results suggest caution should be taken when relating murine studies on bacterial lysates to humans. Furthermore, our data shed light on how a standardized bacterial lysate shapes the response through TLR2 and TLR4, which are crucial for immune response, trained immunity, and tolerance.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 346-358"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000199/pdfft?md5=952f550f9df393fabde33cb319bc6a8e&pid=1-s2.0-S1933021924000199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T-cell responses 肠上皮细胞的 MHC II 类抗原呈递可微调细菌反应性 CD4 T 细胞反应。

IF 8 2区医学

Mucosal Immunology Pub Date : 2024-06-01 DOI: 10.1016/j.mucimm.2023.05.001

Cornelia E. Heuberger , Alina Janney , Nicholas Ilott , Alice Bertocchi , Sebastian Pott , Yisu Gu , Mathilde Pohin , Matthias Friedrich , Elizabeth H. Mann , Claire Pearson , Fiona M. Powrie , Johanna Pott , Emily Thornton , Kevin Joseph Maloy

{"title":"MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T-cell responses","authors":"Cornelia E. Heuberger , Alina Janney , Nicholas Ilott , Alice Bertocchi , Sebastian Pott , Yisu Gu , Mathilde Pohin , Matthias Friedrich , Elizabeth H. Mann , Claire Pearson , Fiona M. Powrie , Johanna Pott , Emily Thornton , Kevin Joseph Maloy","doi":"10.1016/j.mucimm.2023.05.001","DOIUrl":"10.1016/j.mucimm.2023.05.001","url":null,"abstract":"<div>Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favors pro- or anti-inflammatory CD4+ T-cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4+ T-cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs. Whilst IEC MHC II expression had little impact on disease severity following Citrobacter rodentium or Helicobacter hepaticus infection, using a colonic IEC organoid-CD4+ T cell co-culture system, we demonstrate that IECs can activate antigen-specific CD4+ T cells in an MHC II-dependent manner, modulating both regulatory and effector Th cell subsets. Furthermore, we assessed adoptively transferred H. hepaticus-specific CD4+ T cells during intestinal inflammation in vivo and report that IEC MHC II expression dampens pro-inflammatory effector Th cells. Our findings indicate that IECs can function as non-conventional antigen-presenting cells and that IEC MHC II expression fine-tunes local effector CD4+ T-cell responses during intestinal inflammation.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 416-430"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000326/pdfft?md5=37e1a6874fd5ea85e955d961e924fd66&pid=1-s2.0-S1933021923000326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses 树突状细胞介导的对隐孢子虫分泌效应因子的反应可促进寄生虫特异性 CD8+ T 细胞反应

IF 8 2区医学

Mucosal Immunology Pub Date : 2024-06-01 DOI: 10.1016/j.mucimm.2024.03.003

Breanne E. Haskins , Jodi A. Gullicksrud , Bethan A. Wallbank , Jennifer E. Dumaine , Amandine Guérin , Ian S. Cohn , Keenan M. O'Dea , Ryan D. Pardy , Maria I. Merolle , Lindsey A. Shallberg , Emma N. Hunter , Jessica H. Byerly , Eleanor J. Smith , Gracyn Y. Buenconsejo , Briana I. McLeod , David A. Christian , Boris Striepen , Christopher A. Hunter

{"title":"Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses","authors":"Breanne E. Haskins , Jodi A. Gullicksrud , Bethan A. Wallbank , Jennifer E. Dumaine , Amandine Guérin , Ian S. Cohn , Keenan M. O'Dea , Ryan D. Pardy , Maria I. Merolle , Lindsey A. Shallberg , Emma N. Hunter , Jessica H. Byerly , Eleanor J. Smith , Gracyn Y. Buenconsejo , Briana I. McLeod , David A. Christian , Boris Striepen , Christopher A. Hunter","doi":"10.1016/j.mucimm.2024.03.003","DOIUrl":"10.1016/j.mucimm.2024.03.003","url":null,"abstract":"<div>Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, Cryptosporidium was engineered to express a parasite effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized by T cell receptor transgenic OT-I(OVA-TCR-I) clusters of differentiation (CD)8+ T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8+ T cells that were a source of interferon-gamma (IFN-γ) that could restrict growth of Cryptosporidium. This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (rhoptry protein 1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells, type 1 conventional dendritic cells were required to generate CD8+ T cell responses to these model antigens. These data sets highlight Cryptosporidium effectors as potential targets of the immune system and suggest that crosstalk between enterocytes and type 1 conventional dendritic cells is crucial for CD8+ T cell responses to Cryptosporidium.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 387-401"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000229/pdfft?md5=a9bd515cf942f6de6950501be580bb73&pid=1-s2.0-S1933021924000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140154533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanotransduction-induced interplay between phospholamban and yes-activated protein induces smooth muscle cell hypertrophy 机械传导诱导磷脂酰班和是激活蛋白之间的相互作用诱导平滑肌细胞肥大

IF 8 2区医学

Mucosal Immunology Pub Date : 2024-06-01 DOI: 10.1016/j.mucimm.2024.02.007

Renee Rawson , Loan Duong , Eugene Tkachenko , Austin W.T. Chiang , Kevin Okamoto , Ranjan Dohil , Nathan E. Lewis , Richard Kurten , Edsel M. Abud , Seema S. Aceves

{"title":"Mechanotransduction-induced interplay between phospholamban and yes-activated protein induces smooth muscle cell hypertrophy","authors":"Renee Rawson , Loan Duong , Eugene Tkachenko , Austin W.T. Chiang , Kevin Okamoto , Ranjan Dohil , Nathan E. Lewis , Richard Kurten , Edsel M. Abud , Seema S. Aceves","doi":"10.1016/j.mucimm.2024.02.007","DOIUrl":"10.1016/j.mucimm.2024.02.007","url":null,"abstract":"<div>The gastrointestinal system is a hollow organ affected by fibrostenotic diseases that cause volumetric compromise of the lumen via smooth muscle hypertrophy and fibrosis. Many of the driving mechanisms remain unclear. Yes-associated protein-1 (YAP) is a critical mechanosensory transcriptional regulator that mediates cell hypertrophy in response to elevated extracellular rigidity. In the type 2 inflammatory disorder, eosinophilic esophagitis (EoE), phospholamban (PLN) can induce smooth muscle cell hypertrophy. We used EoE as a disease model for understanding a mechanistic pathway in which PLN and YAP interact in response to rigid extracellular substrate to induce smooth muscle cell hypertrophy. PLN-induced YAP nuclear sequestration in a feed-forward loop caused increased cell size in response to a rigid substrate. This mechanism of rigidity sensing may have previously unappreciated clinical implications for PLN-expressing hollow systems such as the esophagus and heart.</div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 315-322"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000163/pdfft?md5=d070e31859976efba722c437889d52bb&pid=1-s2.0-S1933021924000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0