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

ABSTRACT 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.

Download full-text


Available from: Hong-Erh Liang, Jun 11, 2014
16 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Group 2 innate lymphoid cells (ILC2s) play critical roles in anti-helminth immunity, airway epithelial repair, and metabolic homeostasis. Recently, these cells have also emerged as key players in the development of allergic inflammation at multiple barrier surfaces. ILC2s arise from common lymphoid progenitors in the bone marrow, are dependent on the transcription factors RORα, GATA3, and TCF-1, and produce the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, and/or IL-13. The epithelial cell-derived cytokines IL-25, IL-33, and TSLP regulate the activation and effector functions of ILC2s, and recent studies suggest that their responsiveness to these cytokines and other factors may depend on their tissue environment. In this review, we focus on recent advances in our understanding of the various factors that regulate ILC2 function in the context of immunity, inflammation, and tissue repair across multiple organ systems. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor perspectives in biology 01/2015; 7(5). DOI:10.1101/cshperspect.a016337 · 8.68 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis, and pathologic inflammation. Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions. Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation.Journal of Investigative Dermatology advance online publication, 23 October 2014; doi:10.1038/jid.2014.401.
    Journal of Investigative Dermatology 10/2014; 135(3). DOI:10.1038/jid.2014.401 · 7.22 Impact Factor
  • Source
    • "Innate lymphoid cells (ILCs) are identified by their lack of cell lineage markers associated with T cells, B cells, dendritic cells, monocyte/macrophages, and granulocytes, and their expression of CD127 (IL-7Rα), among others [1]–[4]. It is now known that there are 3 major subsets of ILCs, termed ILC1, ILC2 and ILC3, that each have specific cytokine profiles driven by discrete transcription factors [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since innate lymphoid cells (ILCs) have been found to play a role in the immune response to helminth parasites in rodents, we sought to determine their role in human helminth infection. By developing multicolor flow cytometry-based methods to identify and enumerate circulating ILCs and their subsets, we were able to identify a subset of cKit+ ILCs defined as Lineage (Lin)-/CD45+/cKit+/CD127+ that were significantly expanded in the filarial-infected individuals (p = 0.0473) as were those cKit+ ILCs that produced IL-13. Additionally, the frequency of these cKit+ ILCs correlated with the frequency of IL-17 producing CD4+ T cells (Th17 cells; p = 0.025). To investigate the function of cKit+ ILCs, sorted, highly purified human ILCs were subjected to transcriptional profiling by RNAseq and compared to appropriate control cells. These cKit+ ILCs expressed TLRs, a broad range of cytokines/cytokine receptors and MHC Class II molecules suggesting that these ILCs sense pathogens independent of other cell types. Functional analysis revealed expanded cKit+ ILC-specific transcription and ILC-specific microRNA precursors.
    PLoS ONE 09/2014; 9(9):e108649. DOI:10.1371/journal.pone.0108649 · 3.23 Impact Factor
Show more