30
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      The neuropeptide Neuromedin U stimulates innate lymphoid cells and type 2 inflammation

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 play critical roles in stimulating innate and adaptive immune responses required for resistance to helminth infection and promotion of allergic inflammation, metabolic homeostasis and tissue repair 13 . Group 2 innate lymphoid cells (ILC2s) are a potent source of type 2 cytokines and while significant advances have been made in understanding the cytokine milieu that promotes ILC2 responses 49 , there are fundamental gaps in knowledge regarding how ILC2 responses are regulated by other stimuli. In this report, we demonstrate that ILC2s in the gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU) 10, 11 . In contrast to other hematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation and secretion of type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gαq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1 −/− mice compared to control mice. Further, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU-NMUR1 neuronal signaling circuit provides a selective and previously unrecognized mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites.

          Related collections

          Most cited references22

          • Record: found
          • Abstract: found
          • Article: not found

          Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161.

          Innate lymphoid cells (ILCs) are emerging as a family of effectors and regulators of innate immunity and tissue remodeling. Interleukin 22 (IL-22)- and IL-17-producing ILCs, which depend on the transcription factor RORγt, express CD127 (IL-7 receptor α-chain) and the natural killer cell marker CD161. Here we describe another lineage-negative CD127(+)CD161(+) ILC population found in humans that expressed the chemoattractant receptor CRTH2. These cells responded in vitro to IL-2 plus IL-25 and IL-33 by producing IL-13. CRTH2(+) ILCs were present in fetal and adult lung and gut. In fetal gut, these cells expressed IL-13 but not IL-17 or IL-22. There was enrichment for CRTH2(+) ILCs in nasal polyps of chronic rhinosinusitis, a typical type 2 inflammatory disease. Our data identify a unique type of human ILC that provides an innate source of T helper type 2 (T(H)2) cytokines.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Transcriptional Programs Define Molecular Characteristics of Innate Lymphoid Cell Classes and Subsets

              The diversity of innate lymphoid cells (ILCs) is rapidly expanding. Three ILC classes have emerged, ILC1, ILC2, and ILC3, with ILC1 and ILC3 including several subsets. The classification of some subsets is unclear and it remains controversial whether NK cells and ILC1 are distinct cell types. To address these issues, we analyzed ILCs and NK cells gene expression within mouse small intestine, spleen, and liver, as part of the Immunological Genome Project. Results identify unique gene-expression patterns for some ILCs and overlapping patterns between ILC1 and NK cells, whereas few ILC subsets remain indistinguishable. A transcriptional program shared by small intestine ILCs and a core ILC signature is identified. Transcripts that suggest novel ILC functions and developmental paths are revealed and discussed.
                Bookmark

                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                26 April 2018
                06 September 2017
                14 September 2017
                30 July 2018
                : 549
                : 7671
                : 282-286
                Affiliations
                [1 ]Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
                [2 ]Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark
                [3 ]Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
                [4 ]School of Electrical and Computer Engineering, Cornell University, Ithaca, NY 14853, USA
                [5 ]Institute of Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany
                [6 ]Columbia Center for Translational Immunology and Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA
                [7 ]Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA
                Author notes
                [* ] Corresponding author: David Artis, Ph.D. Weill Cornell Medicine, Cornell University, Joan and Sanford I. Weill Department of Medicine, Belfer Research Building, Room 724 (box 210), 413 East 69 th Street, New York, NY 10021, USA, Tel: 1-646-962-6291, dartis@ 123456med.cornell.edu
                Article
                NIHMS896443
                10.1038/nature23676
                6066372
                28869965
                fd00d694-097f-4fc7-a636-9334b96f0e26

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article