IL-17 producing gammadelta T cells are required for a controlled inflammatory response after bleomycin-induced lung injury

Inflammation. 2008 Jun;31(3):167-79. doi: 10.1007/s10753-008-9062-6. Epub 2008 Mar 13.

Abstract

Background: gammadelta T cells play a key role in the regulation of inflammatory responses in epithelial tissue, and in adaptive immunity, as gammadelta T cell deficient mice have a severely impaired capacity to clear lung pathogens. gammadelta T cells regulate the initial inflammatory response to microbial invasion and thereby protect against tissue injury. Here we examined the response of gammadelta T cells to lung injury induced by bleomycin, in an effort to study the inflammatory response in the absence of any adaptive immune response to a pathogen.

Results: After lung injury by bleomycin, we localized the gammadelta T cells to the lung lesions. gammadelta T cells were the predominant source of IL-17 (as detected by flow cytometry and real-time PCR). Moreover, gammadelta T cell knockout mice showed a significant reduction in cellular infiltration into the airways, reduced expression of IL-6 in the lung, and a significant delay in epithelial repair.

Conclusion: Mouse gammadelta T cells produce IL-17 in response to lung injury and are required for an organized inflammatory response and epithelial repair. The lack of gammadelta T cells correlates with increased inflammation and fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin
  • Cell Proliferation
  • Collagen / metabolism
  • Disease Models, Animal
  • Flow Cytometry
  • Interleukin-17 / metabolism*
  • Interleukin-6 / metabolism
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Lymphocyte Subsets / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Respiratory Mucosa / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • Interleukin-17
  • Interleukin-6
  • Receptors, Antigen, T-Cell, gamma-delta
  • Bleomycin
  • Collagen