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Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice
Open accessAbstract
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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“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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Metadata
- 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
- Publisher
- Rockefeller University Press
- Published
- 2011-07-11
- Volume
- 208
- Issue
- 8
- Pages
- 1707-1719
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3149214
- 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
- green
- www.ncbi.nlm.nih.gov
- 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 › Rheumatology › 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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