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Title: Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice
Authors: Oh, K.
Park, H-B.
Byoun, O-J.
Shin, D-M.
Jeong, E. M.
Kim, Y. W.
Kim, Y. S.
Melino, Gerry
Kim, I-G.
Lee, D-S.
First Published: 11-Jul-2011
Publisher: Rockefeller University Press
Citation: Journal of Experimental Medicine Vol. 208 No. 8 1707-1719
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.
DOI Link: 10.1084/jem.20101457
ISSN: 0022-1007
eISSN: 1540-9538
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at
Description: Supplemental Material can be found at:
Appears in Collections:Published Articles, MRC Toxicology Unit

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