Systemically dispersed innate IL-13-expressing cells in type 2 immunity

Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, CA 94143-0795, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2010; 107(25):11489-94. DOI: 10.1073/pnas.1003988107
Source: PubMed


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.

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Available from: Hong-Erh Liang, Jun 11, 2014
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    • "and data not shown). In this regard, the Lin À GFP hi IL-17RB + c-Kitˉ cells detected in our murine model of food allergy appeared identical to the intestinal IL-25-responding ILC2s that have previously been shown to elicit protective immunity against intestinal worm infection (Moro et al., 2010; Neill et al., 2010; Price et al., 2010; Saenz et al., 2010). In contrast, MMC9s did not respond to IL-25 stimulation in vitro and in vivo and are distinct from both ILC2s and the previously reported IL-25-elicited c-Kit int -GFP + multipotent progenitor (MPP type2 ) (Saenz et al., 2010). "
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    Immunity 09/2015; 43(4). DOI:10.1016/j.immuni.2015.08.020 · 21.56 Impact Factor
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    • "These original studies showed that IL-25-and IL-33-responsive ILC2s were critical for the development of type 2 cytokine – associated inflammation and goblet cell hyperplasia that facilitate expulsion of N. brasiliensis in the absence of adaptive immunity (Moro et al. 2010; Neill et al. 2010; Price et al. 2010). A more recent study has shown that IL-33 is critical for the induction of IL-13 production by ILC2s to mediate worm expulsion (Hung et al. 2013). "
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    Cold Spring Harbor perspectives in biology 01/2015; 7(5). DOI:10.1101/cshperspect.a016337 · 8.68 Impact Factor
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    • "ILC2s were originally identified in the gut and associated lymphoid tissues and found to contribute to immunity to helminth parasites in the absence of the adaptive immune system (Fort et al., 2001; Schmitz et al., 2005; Fallon et al., 2006; Moro et al., 2010; Neill et al., 2010; Price et al., 2010). "
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