IFN-γ production by innate immune cells is sufficient for development of hypersensitivity pneumonitis

Stephanie Nance, Richard Cross, Ae-Kyung Yi, Elizabeth Fitzpatrick

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The disease is characterized by lymphocytic alveolitis, granuloma formation and fibrosis. IFN-γ is required for the formation of granulomas in HP, and we therefore focused on identifying the cellular sources of IFN-γ during the disease. Using the Saccharopolyspora rectivirgula (SR) animal model of HP, we demonstrated that the majority of IFN-γ+ cells in the lung following SR exposure are neutrophils. Ab-mediated depletion of neutrophils in mice prior to exposure to SR resulted in a decrease in the level of IFN-γ mRNA and protein compared to isotype Ab-treated mice, suggesting that neutrophils are an important source of IFN-γ during HP. To determine the contribution of T and non-T cell sources of IFN-γ to granuloma formation, we performed adoptive transfer studies. RAG-1-/- mice reconstituted with spleen cells from IFN-γ-/- mice developed granulomas similarly to RAG-1-/- mice reconstituted with normal spleen cells. Therefore innate immune cell IFN-γ production in the absence of T cell IFN-γ production is sufficient for granuloma formation. These results provide new insight into the pathogenesis of HP and demonstrate the important contribution of innate immune cells to the disease process.

Original languageEnglish (US)
Pages (from-to)1928-1938
Number of pages11
JournalEuropean Journal of Immunology
Volume35
Issue number6
DOIs
StatePublished - Jun 1 2005

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Extrinsic Allergic Alveolitis
Granuloma
Saccharopolyspora
Neutrophils
Spleen
Adoptive Transfer
Interstitial Lung Diseases
Fibrosis
Animal Models
T-Lymphocytes
Antigens
Lung
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology

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IFN-γ production by innate immune cells is sufficient for development of hypersensitivity pneumonitis. / Nance, Stephanie; Cross, Richard; Yi, Ae-Kyung; Fitzpatrick, Elizabeth.

In: European Journal of Immunology, Vol. 35, No. 6, 01.06.2005, p. 1928-1938.

Research output: Contribution to journalArticle

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