TY - JOUR
T1 - Vaccinia vaccine-based immunotherapy arrests and reverses established pulmonary fibrosis
AU - Collins, Samuel L.
AU - Chan-Li, Yee
AU - Oh, Min Hee
AU - Vigeland, Christine L.
AU - Limjunyawong, Nathachit
AU - Mitzner, Wayne
AU - Powell, Jonathan D.
AU - Horton, Maureen R.
N1 - Publisher Copyright:
© 2016 American Society for Clinical Investigation. All rights reserved.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.83116
DO - 10.1172/jci.insight.83116
M3 - Article
AN - SCOPUS:84991780096
SN - 2379-3708
VL - 1
JO - JCI Insight
JF - JCI Insight
IS - 4
M1 - A48
ER -