Vaccinia vaccine–based immunotherapy arrests and reverses established pulmonary fibrosis

• DOI: 10.1172/jci.insight.83116
• Publication Date: 2016-04-06T18:00:45Z
• Authors: Samuel L. Collins; Yee Chan-Li; MinHee Oh; Christine L. Vige...; Nathachit Limjuny...; Wayne Mitzner; Jonathan D. Powell; Maureen R. Horton
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

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.