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Vaccinia vaccine–based immunotherapy arrests and reverses established pulmonary fibrosis
Samuel L. Collins, … , Jonathan D. Powell, Maureen R. Horton
Samuel L. Collins, … , Jonathan D. Powell, Maureen R. Horton
Published April 7, 2016
Citation Information: JCI Insight. 2016;1(4):e83116. https://doi.org/10.1172/jci.insight.83116.
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Research Article Inflammation Pulmonology

Vaccinia vaccine–based immunotherapy arrests and reverses established pulmonary fibrosis

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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

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Figure 1

Immunotherapy with vaccinia vaccine inhibits the development of pulmonary fibrosis.

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Immunotherapy with vaccinia vaccine inhibits the development of pulmonar...
(A) Day-42 total lung cell numbers of mice treated with i.p. bleomycin and either i.n. PBS or vaccinia vaccine on day 14. (B) Flow cytometric analysis of total lung CD4+ T cells, CD11b+ cells, and Gr1+ cells. (C) Intracellular cytokine analysis of total lung IFNG+, IL17+, and FoxP3+ CD4+ T cells. Histological analysis of lungs 42 days following i.p. bleomycin. (D) H&E staining of lung sections at ×20 (left panels) and ×100 (right panels) magnification. (E) Masson’s trichrome staining of lung sections at ×100 magnification. (F) Total lung collagen 42 days following i.p. bleomycin. Error bars represent one standard deviation of the mean. Experiments were performed 3 times with 10 mice per group. Paired Student’s t tests were performed with Bonferroni correction when indicated.

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