title: 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.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Collins
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yee
authors.initials: Y
authors.lastname: Chan-Li
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: MinHee
authors.initials: M
authors.lastname: Oh
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Vigeland
authors.affiliation: Department of Environmental Health Sciences, Program in Respiratory Biology and Lung Diseases, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Nathachit
authors.initials: N
authors.lastname: Limjunyawong
authors.affiliation: Department of Environmental Health Sciences, Program in Respiratory Biology and Lung Diseases, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Powell
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Horton