التفاصيل البيبلوغرافية
العنوان:
Fibroblast-specific integrin-alpha V differentially regulates type 17 and type 2 driven inflammation and fibrosis
المؤلفون:
Neil C. Henderson , Joshua Sciurba , Kevin M. Vannella , Nikhil Jiwrajka , Erik P. Karmele , Kevin M. Hart , Sandra White , Jamie L Redes , Thomas A. Wynn , Richard L. Gieseck
المصدر:
Sciurba, J C, Gieseck, R L, Jiwrajka, N, White, S D, Karmele, E P, Redes, J, Vannella, K M, Henderson, N C, Wynn, T A & Hart, K M 2018, ' Fibroblast-specific integrin alpha V differentially regulates type 17 and type 2 driven inflammation and fibrosis ', The Journal of Pathology . https://doi.org/10.1002/path.5215
سنة النشر:
2018
مصطلحات موضوعية:
0301 basic medicine , Liver Cirrhosis , Male , Pulmonary Fibrosis , Population , Integrin , Alpha (ethology) , Inflammation , Integrin alpha5 , Pathology and Forensic Medicine , 03 medical and health sciences , 0302 clinical medicine , Immune system , Fibrosis , medicine , Animals , Fibroblast , education , Mice, Knockout , education.field_of_study , Interleukin-13 , biology , business.industry , Fibroblasts , medicine.disease , Asthma , Disease Models, Animal , 030104 developmental biology , medicine.anatomical_structure , 030220 oncology & carcinogenesis , Knockout mouse , Cancer research , biology.protein , Female , medicine.symptom , business , Gene Deletion
الوصف:
Fibroproliferative diseases affect a significant proportion of the world's population. Despite this, core mechanisms driving organ fibrosis of diverse etiologies remain ill defined. Recent studies suggest that integrin-alpha V serves as a master driver of fibrosis in multiple organs. Although diverse mechanisms contribute to the progression of fibrosis, TGF-β and IL-13 have emerged as central mediators of fibrosis during type 1/type 17, and type 2 polarized inflammatory responses, respectively. To investigate if integrin-alpha V interactions or signaling is critical to the development of type 2 fibrosis, we analyzed fibroblast-specific integrin-alpha V knockout mice in three type 2-driven inflammatory disease models. While we confirmed a role for integrin-alpha V in type 17-associated fibrosis, integrin-alpha V was not critical to the development of type 2-driven fibrosis. Additionally, our studies support a novel mechanism through which fibroblasts, via integrin-alpha V expression, are capable of regulating immune polarization. We show that when integrin-alpha V is deleted on fibroblasts, initiation of type 17 inflammation is inhibited leading to a deregulation of type 2 inflammation. This mechanism is most evident in a model of severe asthma, which is characterized by a mixed type 2/type 17 inflammatory response. Together, these findings suggest dual targeting of integrin-alpha V and type 2 pathways may be needed to ameliorate fibrosis and prevent rebound of opposing pro-fibrotic and inflammatory mechanisms. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
وصف الملف:
application/pdf
تدمد:
1096-9896
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56fb10829f9d9099aa528881451e6db4 https://pubmed.ncbi.nlm.nih.gov/30536905
حقوق:
OPEN
رقم الأكسشن:
edsair.doi.dedup.....56fb10829f9d9099aa528881451e6db4
قاعدة البيانات:
OpenAIRE
