title: Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice.
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.
authors: Laboratory of Immunology, Department of Biomedical Sciences / Transplantation Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors: Keunhee
authors: K
authors: Oh
authors: Hyung-Bae
authors: HB
authors: Park
authors: Ok-Jin
authors: OJ
authors: Byoun
authors: Dong-Myung
authors: DM
authors: Shin
authors: Eui Man
authors: EM
authors: Jeong
authors: Young Whan
authors: YW
authors: Kim
authors: Yon Su
authors: YS
authors: Kim
authors: Gerry
authors: G
authors: Melino
authors: In-Gyu
authors: IG
authors: Kim
authors: Dong-Sup
authors: DS
authors: Lee
mesh_terms: D000588:Amines / Q000032:analysis; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000032:analysis; D001761:Bleomycin / Q000633:toxicity; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D003094:Collagen / Q000032:analysis; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006652:Histological Techniques; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012313:RNA / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
chemical_list: D000588:Amines; D017931:DNA Primers; D020381:Interleukin-17; D015850:Interleukin-6; D001761:Bleomycin; C076022:5-(biotinamido)pentylamine; D012313:RNA; D001710:Biotin; D003094:Collagen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins