Fibroblast-specific integrin-alpha V differentially regulates type 17 and type 2 driven inflammation and fibrosis
| Autor: | 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 |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | 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 |
| ISSN: | 1096-9896 |
| DOI: | 10.1002/path.5215 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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