P124 Immunotherapy in the form of intranasal vaccinia vaccination induces tissue resident memory cells that arrest and reverse pulmonary fibrosis
Year: 2016
Type: conference-abstract
Abstract: Idiopathic pulmonary fibrosis is a fatal disease with no 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 play a role in regulating the unremitting inflammation that promotes lung fibrosis. In an effort to determine if immunotherapy, in the form of intranasal vaccinia vaccination, can treat/reverse the disease process, we utilized a model of intraperitoneal injections of bleomycin over four weeks to induce progressive lung fibrosis by day 72. We assess the effect of immunotherapy on fibrosis by histology, cellular infiltrate, cytokine expression, fibrocyte recruitment and pulmonary function. We demonstrate that the induction of a lung Th1 response with intranasal vaccinia vaccination, after lung fibrosis has already been established by repeated injections of intraperitoneal bleomycin, is effective at arresting and reversing established fibrosis as measured by decreased lung collagen, lung fibrocytes, histologic injury and improved lung physiologic function (F1). Mechanistically, the interruption and reversal of fibrosis is mediated by Trm cells that regulate the tissue specific immune microenvironment by promoting anti-fibrotic immune responses (F2a,b). Furthermore, prevention of vaccinia-induced lung Trm cells abrogates the reversal of fibrosis (F2c). These data not only have implications for the development of novel 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.
Source: QJM
Institution: Johns Hopkins University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2807298409