Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and γδ T cells

Steven J. Van Dyken, Alexander Mohapatra, Jesse C. Nussbaum, Ari B. Molofsky, Emily E. Thornton, Steven F. Ziegler, Andrew N.J. McKenzie, Matthew F. Krummel, Hong Erh Liang, Richard M. Locksley

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

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 Tcells, 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.

Original languageEnglish
Pages (from-to)414-424
Number of pages11
JournalImmunity
Volume40
Issue number3
DOIs
StatePublished - Mar 20 2014

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