Cited by 118Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisTransplantation: Methods and OutcomesSystemic Sclerosis and Related Diseases

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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Oh, Keunhee, Park, Hyung-Bae, Byoun, Ok-Jin, Shin, Dong-Myung, Jeong, Eui Man, Kim, Young Whan, Kim, Yon Su, Melino, Gerry +2 more·2011·Journal of Experimental Medicine

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.

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  • Alarmin cytokines TSLP, IL-25, and IL-33 initiate type 2-dependent fibrosis by triggering production of IL-4 and IL-13 in innate lymphoid cells, T cells, eosinophils, and other type 2-associated leukocytes.

    “the alarmin cytokines thymic stromal lymphopoietin, IL-25, and IL-33 function as key initiators of type 2-dependent fibrosis by triggering the production of IL-4 and IL-13 in innate lymphoid cells, T cells, eosinophils, and other type 2-associated leukocytes129–132”

    From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [130]

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Authors
Oh, K., Park, H.-B., Byoun, O.-J., Shin, D.-M., Jeong, E. M., Kim, Y. W., Kim, Y. S., Melino, G., Kim, I.-G., & Lee, D.-S.
Affiliations
  • Seoul National University (KR)
  • University of Leicester (GB)
Corresponding author
  • Kim, In-Gyu
  • Lee, Dong-Sup
Venue
Journal of Experimental Medicine
Published
2011-07-11
Volume
208
Issue
8
Pages
1707-1719
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2139169478
Cited by
118
References
47
Citations by year
2026: 5 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 14 · 2012: 8
FWCI
9.25
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Leicester Research Archive (University of Leicester) (submittedVersion, cc-by-nc-sa)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
Keywords
IL-17, T cell differentiation, pulmonary fibrosis, bleomycin-induced lung injury, IL-6 secretion, lung epithelial cells, lung inflammation, TGF-beta, bone marrow chimeras, fibrogenesis
MeSH terms
Protein Glutamine gamma Glutamyltransferase 2, Amines, Animals, Biotin, Bleomycin, Collagen, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Flow Cytometry, Fluorescent Antibody Technique, Histological Techniques, Male, Mice, Inbred C57BL, Pneumonia, Transglutaminases, Pulmonary Fibrosis, RNA, T-Lymphocytes, Blotting, Western, Interleukin-6, Polymerase Chain Reaction, DNA Primers, Mice, Knockout, Bronchoalveolar Lavage, GTP-Binding Proteins, Interleukin-17, Mice

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