Vaccinia vaccine-based immunotherapy arrests and reverses established pulmonary fibrosis.

Abstract

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.

• Authors: Samuel L Collins, Yee Chan-Li, MinHee Oh, Christine L Vigeland, Nathachit Limjunyawong, Wayne Mitzner, Jonathan D Powell, Maureen R Horton
• Journal: JCI insight (JCI Insight) Vol. 1 Issue 4 Pg. e83116 (Apr 07 2016) ISSN: 2379-3708 [Print] United States
• PMID: 27158671 (Publication Type: Journal Article)