title: Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and γδ T cells.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Dyken
authors.affiliation: Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mohapatra
authors.affiliation: Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Nussbaum
authors.affiliation: Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Thornton
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
authors.affiliation: Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Hong-Erh
authors.initials: HE
authors.lastname: Liang
authors.affiliation: Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: locksley@medicine.ucsf.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D002686:Chitin / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D002686:Chitin