Systemically dispersed innate IL-13-expressing cells in type 2 immunity.
Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the contributions by innate cells in initiating adaptive immunity, including a novel lineage-negative population of cells that secretes IL-13 and IL-5 in response to the epithelial cytokines IL-25 and IL-33. Here, we use IL-4 and IL-13 reporter mice to track lineage-negative innate cells that arise during type 2 immunity or in response to IL-25 and IL-33 in vivo. Unexpectedly, lineage-negative IL-25 (and IL-33) responsive cells are widely distributed in tissues of the mouse and are particularly prevalent in mesenteric lymph nodes, spleen, and liver. These cells expand robustly in response to exogenous IL-25 or IL-33 and after infection with the helminth Nippostrongylus brasiliensis, and they are the major innate IL-13-expressing cells under these conditions. Activation of these cells using IL-25 is sufficient for worm clearance, even in the absence of adaptive immunity. Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses.
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, CA 94143-0795, USA.
April E
AE
Price
Hong-Erh
HE
Liang
Brandon M
BM
Sullivan
R Lee
RL
Reinhardt
Chris J
CJ
Eisley
David J
DJ
Erle
Richard M
RM
Locksley
D000818:Animals; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000469:parasitology; D007107:Immune System; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000737:chemistry* / Q000378:metabolism; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000378:metabolism / Q000472:pathogenicity*
D016207:Cytokines; C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D007378:Interleukins; C442281:Mydgf protein, mouse; D015847:Interleukin-4