J Exp Med-2011-Oh-1707-19.pdf (3.26 MB)

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

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posted on 22.04.2016 by K. Oh, H-B. Park, O-J. Byoun, D-M. Shin, E. M. Jeong, Y. W. Kim, Y. S. Kim, Gerry Melino, I-G. Kim, D-S. Lee
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.
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Funding

This work was supported by grants from MarineBio Technology Project, Ministry of Land, Transport, and Maritime Affairs (D-S. Lee) and Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs (D-S. Lee; nos. A10019010110000100 and A08402210210000400).

History

Citation

Journal of Experimental Medicine Vol. 208 No. 8 1707-1719

Version

VoR (Version of Record)

Published in

Journal of Experimental Medicine Vol. 208 No. 8 1707-1719

Publisher

Rockefeller University Press

issn

0022-1007

eissn

1540-9538

Acceptance date

09/06/2011

Available date

22/04/2016

Publisher version

http://jem.rupress.org/content/208/8/1707

Notes

Supplemental Material can be found at: http://jem.rupress.org/content/suppl/2011/07/10/jem.20101457.DC1.html

Language

en

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