ARTICLE: Vaccinia vaccine–based immunotherapy arrests and reverses established pulmonary fibrosis
AUTHORS: Samuel L. Collins, Yee Chan-Li, MinHee Oh, Christine L. Vigeland, Nathachit Limjunyawong, Wayne Mitzner, Jonathan D. Powell and Maureen R. Horton
JOURNAL: JCI Insight. 2016 Apr 7; 1(4): e83116
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.
For a link to the full article, click here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855513/