| First Author | Collins SL | Year | 2016 |
| Journal | JCI Insight | Volume | 1 |
| Issue | 4 | Pages | e83116 |
| PubMed ID | 27158671 | Mgi Jnum | J:290963 |
| Mgi Id | MGI:6442864 | Doi | 10.1172/jci.insight.83116 |
| Citation | Collins SL, et al. (2016) Vaccinia vaccine-based immunotherapy arrests and reverses established pulmonary fibrosis. JCI Insight 1(4):e83116 |
| abstractText | Idiopathic pulmonary fibrosis (IPF) is a fatal disease without any cure. Both human disease and animal models demonstrate dysregulated wound healing and unregulated fibrogenesis in a background of low-grade chronic T lymphocyte infiltration. Tissue-resident memory T cells (Trm) are emerging as important regulators of the immune microenvironment in response to pathogens, and we hypothesized that they might play a role in regulating the unremitting inflammation that promotes lung fibrosis. Herein, we demonstrate that lung-directed immunotherapy, in the form of i.n. vaccination, induces an antifibrotic T cell response capable of arresting and reversing lung fibrosis. In mice with established lung fibrosis, lung-specific T cell responses were able to reverse established pathology - as measured by decreased lung collagen, fibrocytes, and histologic injury - and improve physiologic function. Mechanistically, we demonstrate that this effect is mediated by vaccine-induced lung Trm. These data not only have implications for the development of immunotherapeutic regimens to treat IPF, but also suggest a role for targeting tissue-resident memory T cells to treat other tissue-specific inflammatory/autoimmune disorders. |
