TY - JOUR
T1 - Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and γδ T cells
AU - Van Dyken, Steven J.
AU - Mohapatra, Alexander
AU - Nussbaum, Jesse C.
AU - Molofsky, Ari B.
AU - Thornton, Emily E.
AU - Ziegler, Steven F.
AU - McKenzie, Andrew N.J.
AU - Krummel, Matthew F.
AU - Liang, Hong Erh
AU - Locksley, Richard M.
N1 - Funding Information:
We thank S. Akira (Osaka University), J. Ihle (St. Jude), and M. Steinhoff (UCSF) for mice, D. Sheppard, C. Lowell, and D. Erle for helpful comments on the manuscript, and Z. Wang, N. Flores, and M. Consengco for expert technical assistance. This work was supported by National Institutes of Health grants AI026918, AI030663, and HL107202, Howard Hughes Medical Institute, and the Sandler Asthma Basic Research Center at the University of California, San Francisco.
PY - 2014/3/20
Y1 - 2014/3/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896332584&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.02.003
DO - 10.1016/j.immuni.2014.02.003
M3 - Article
C2 - 24631157
AN - SCOPUS:84896332584
VL - 40
SP - 414
EP - 424
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -