Regulation of pulmonary inflammation and fibrosis through expression of integrins αVβ3 and αVβ5 on pulmonary T lymphocytes

Irina G. Luzina, Nevins W. Todd, Natalia Nacu, Virginia Lockatell, Jung Choi, Laura K. Hummers, Sergei P. Atamas

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. Pulmonary diseases associated with fibrosis, including scleroderma lung disease, are characterized by the accumulation of T cells in the lungs. These cells are thought to facilitate lung fibrosis, but the exact mechanisms of their profibrotic action are not clear. Several αV-containing integrins, including αVβ3 and αVβ5, have been shown to directly activate transforming growth factor β (TGFβ) and promote collagen accumulation. The aim of this study was to investigate whether pulmonary T cells express profibrotic integrins and regulate collagen accumulation. Methods. Expression of integrins was assessed by immunohistochemical analysis of lung tissue, by flow cytometry using bronchoalveolar lavage fluid from patients with systemic sclerosis (SSc), and in a CCL18 overexpression animal model of pulmonary T cell infiltration. Experiments in cell cultures were performed to determine whether integrin-expressing T cells are profibrotic in cocultures with pulmonary fibroblasts and, if so, through what possible mechanism. Results. Lymphocytes and integrin-positive cells were present in the lungs, and pulmonary T cells expressed integrins αVβ3 and αVβ5 in patients with SSc and in the animal model. Systemic administration of neutralizing anti-integrin αV antibody or a genetic deficiency of integrin β3 in the CCL18 overexpression model significantly attenuated CCL18-driven pulmonary lymphocytic infiltration and collagen accumulation. Jurkat T cells overexpressing integrin αVβ3 or integrin αVβ5 in cocultures with primary pulmonary fibroblasts stimulated collagen accumulation and Smad2 nuclear translocation. Neutralizing anti-TGFβ antibody attenuated the profibrotic effect of integrin-expressing T cells. Conclusion. Pulmonary infiltrating T lymphocytes may express integrins αVβ3 and αVβ5 that are necessary for lymphocytic infiltration and T cell-associated TGFβ activation and collagen accumulation.

Original languageEnglish (US)
Pages (from-to)1530-1539
Number of pages10
JournalArthritis and rheumatism
Volume60
Issue number5
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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