IL-1 and IL-23 Mediate Early IL-17A Production in Pulmonary Inflammation Leading to Late Fibrosis
Open accessAbstract
BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.
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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 [132]
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- Authors
- Gasse, P., Riteau, N., Vacher, R., Michel, M.-L., Fautrel, A., di Padova, F., Fick, L., Charron, S., Lagente, V., Eberl, G., Le Bert, M., Quesniaux, V. F. J., Huaux, F., Leite-de-Moraes, M., Ryffel, B., & Couillin, I.
- Affiliations
- Université d'Orléans (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Cape Town (ZA)
- UCLouvain (BE)
- Corresponding author
- Couillin, Isabelle
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-08-16
- Volume
- 6
- Issue
- 8
- Pages
- e23185
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3156735
- OpenAlex
- W1991268098
- Cited by
- 208
- References
- 47
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 12 · 2023: 12 · 2022: 11 · 2021: 15 · 2020: 14 · 2019: 15 · 2018: 17 · 2017: 15 · 2016: 22 · 2015: 15 · 2014: 14 · 2013: 19 · 2012: 12
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Open University of Cape Town (University of Cape Town) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ludwig Institute for Cancer Research
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- idiopathic pulmonary fibrosis, IL-1β, IL-23, IL-17A, IL-17F, NLRP3 inflammasome, bleomycin-induced lung injury, lung inflammation, γδ T cells, RORγt, TGF-β1, collagen deposition, innate immunity, therapeutic target
- MeSH terms
- Animals, Bleomycin, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Lung, Male, Mice, Inbred C57BL, Mice, Transgenic, Pneumonia, Pulmonary Fibrosis, T-Lymphocyte Subsets, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, Mice, Interleukin-1beta, Interleukin-23, Interleukin-23 Subunit p19, Transforming Growth Factor beta1, Lung Injury
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