دورية أكاديمية
IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ
العنوان: | IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
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المؤلفون: | Yunhao Tan, Kenta Mosallanejad, Qingxiu Zhang, Stephen O’Brien, Meghan Clements, Stuart Perper, Sarah Wilson, Sudiksha Chaulagain, Jing Wang, Mary Abdalla, Helen Al-Saidi, Danyal Butt, Anca Clabbers, Kwasi Ofori, Beth Dillon, Bohdan Harvey, John Memmott, Christopher Negron, David Winarta, Catherine Tan, Amlan Biswas, Feng Dong, Vanessa Morales-Tirado, Xiaoqing Lu, Gurminder Singh, Michael White, Shanna Ashley, Heather Knight, Susan Westmoreland, Lucy Phillips, Tracy Carr, Lauren Reinke-Breen, Rajeeva Singh, Jianwen Xu, Kan Wu, Lisa Rinaldi, Brian Stoll, Yupeng David He, Lisa Hazelwood, Jozsef Karman, Andrew McCluskey, William Stine, Ivan Correia, Stephen Gauld, Marc C. Levesque, Geertruida Veldman, Cedric Hubeau, Timothy Radstake, Ramkrishna Sadhukhan, Edda Fiebiger |
المصدر: | Frontiers in Immunology, Vol 15 (2024) |
بيانات النشر: | Frontiers Media S.A., 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Immunologic diseases. Allergy |
مصطلحات موضوعية: | IL11, fibrosis, drug target, STAT3, ERK, stromal cell, Immunologic diseases. Allergy, RC581-607 |
الوصف: | Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1664-3224 |
Relation: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full; https://doaj.org/toc/1664-3224 |
DOI: | 10.3389/fimmu.2024.1293883 |
URL الوصول: | https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 |
رقم الأكسشن: | edsdoj.6fa4a13cb80640969f85235ea03fd692 |
قاعدة البيانات: | Directory of Open Access Journals |
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