| First Author | Sciurba JC | Year | 2019 |
| Journal | J Pathol | Volume | 248 |
| Issue | 1 | Pages | 16-29 |
| PubMed ID | 30536905 | Mgi Jnum | J:275592 |
| Mgi Id | MGI:6305621 | Doi | 10.1002/path.5215 |
| Citation | Sciurba JC, et al. (2019) Fibroblast-specific integrin-alpha V differentially regulates type 17 and type 2 driven inflammation and fibrosis. J Pathol 248(1):16-29 |
| abstractText | 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-beta 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 (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
