Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice

Keunhee Oh, Hyung Bae Park, Ok Jin Byoun, Dong Myung Shin, Eui Man Jeong, Young Whan Kim, Yon Su Kim, Gerry Melino, In Gyu Kim, Dong Sup Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary fibrosis is a potentially life-threatening disease that may be caused by overt or asymptomatic inflammatory responses. However, the precise mechanisms by which tissue injury is translated into inflammation and consequent fibrosis remain to be established. Here, we show that in a lung injury model, bleomycin induced the secretion of IL-6 by epithelial cells in a transglutaminase 2 (TG2)-dependent manner. This response represents a key step in the differentiation of IL-17-producing T cells and subsequent inflammatory amplification in the lung. The essential role of epithelial cells, but not inflammatory cells, TG2 was confirmed in bone marrow chimeras; chimeras made in TG2-deficient recipients showed reduced inflammation and fibrosis, compared with those in wild-type mice, regardless of the bone marrow cell phenotype. Epithelial TG2 thus appears to be a critical inducer of inflammation after noninfectious pulmonary injury. We further demonstrated that fibroblast-derived TG2, acting downstream of transforming growth factor-β, is also important in the effector phase of fibrogenesis. Therefore, TG2 represents an interesting potential target for therapeutic intervention.

Original languageEnglish
Pages (from-to)1707-1719
Number of pages13
JournalJournal of Experimental Medicine
Volume208
Issue number18
DOIs
Publication statusPublished - Aug 1 2011

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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