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Chitin Activates Parallel Immune Modules that Direct Distinct Inflammatory Responses via Innate Lymphoid Type 2 and γδ T Cells
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Chitin, a polysaccharide constituent of many allergens and parasites, initiates innate type 2 lung inflammation through incompletely defined pathways. We show that inhaled chitin induced expression of three epithelial cytokines, interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP), which nonredundantly activated resident innate lymphoid type 2 cells (ILC2s) to express IL-5 and IL-13 necessary for accumulation of eosinophils and alternatively activated macrophages (AAMs). In the absence of all three epithelial cytokines, ILC2s normally populated the lung but failed to increase IL-5 and IL-13. Although eosinophils and AAMs were attenuated, neutrophil influx remained normal without these epithelial cytokines. Genetic ablation of ILC2s, however, enhanced IL-1β, TNFα, and IL-23 expression, increased activation of IL-17A-producing γδ T cells, and prolonged neutrophil influx. Thus, chitin elicited patterns of innate cytokines that targeted distinct populations of resident lymphoid cells, revealing divergent but interacting pathways underlying the tissue accumulation of specific types of inflammatory myeloid cells.
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“chitin, a long-chain polysaccharide that is a potent type 2 response inducer”
From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Van Dyken et al., 2014
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Metadata
- Authors
- Van Dyken, S. J., Mohapatra, A., Nussbaum, J. C., Molofsky, A. B., Thornton, E. E., Ziegler, S. F., McKenzie, A. N. J., Krummel, M. F., Liang, H.-E., & Locksley, R. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Benaroya Research Institute (US)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Locksley, Richard M.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 40
- Issue
- 3
- Pages
- 414-424
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4019510
- OpenAlex
- W2097384956
- Cited by
- 251
- References
- 53
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 12 · 2023: 16 · 2022: 10 · 2021: 18 · 2020: 15 · 2019: 31 · 2018: 35 · 2017: 20 · 2016: 24 · 2015: 22 · 2014: 25
- FWCI
- 13.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (AI030663, AI026918, HL107202)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Studies on Chitinases and Chitosanases
- Keywords
- chitin, γδ T cells, IL-25, IL-33, thymic stromal lymphopoietin, epithelial cytokines, IL-5, IL-13, eosinophils, M2 macrophages, neutrophil influx, IL-17A, lung inflammation, innate immunity
- MeSH terms
- Animals, Chitin, Eosinophils, Gene Expression Regulation, Immunity, Innate, Inflammation, Lung, Lymphocyte Activation, Macrophage Activation, Macrophages, T-Lymphocyte Subsets, Cytokines, Receptors, Antigen, T-Cell, gamma-delta, Mice, Knockout, Mice
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