title: Cutting Edge: Notch Signaling Promotes the Plasticity of Group-2 Innate Lymphoid Cells.
abstract: The mechanisms underlying lymphocyte lineage stability and plasticity remain elusive. Recent work indicates that innate lymphoid cells (ILC) possess substantial plasticity. Whereas natural ILC2 (nILC2) produce type-2 cytokines, plastic inflammatory ILC2 (iILC2) can coproduce both type-2 cytokines and the ILC3-characteristic cytokine, IL-17. Mechanisms that elicit this lineage plasticity, and the importance in health and disease, remain unclear. In this study we show that iILC2 are potent inducers of airway inflammation in response to acute house dust mite challenge. We find that Notch signaling induces lineage plasticity of mature ILC2 and drives the conversion of nILC2 into iILC2. Acute blockade of Notch signaling abolished functional iILC2, but not nILC2, in vivo. Exposure of isolated nILC2 to Notch ligands inducedRorcexpression and elicited dual IL-13/IL-17 production, converting nILC2 into iILC2. Together these results reveal a novel role for Notch signaling in eliciting ILC2 plasticity and driving the emergence of highly proinflammatory innate lymphocytes.
authors.affiliation: Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208.
authors.forename: Kangning
authors.identifier: 0000-0003-0935-6305
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208.|Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China.
authors.forename: Xingyuan
authors.identifier: 0000-0001-9698-9340
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Albany Medical College, Albany, NY 12203.
authors.forename: Muhammad Asghar
authors.identifier: 0000-0003-4321-4992
authors.initials: MA
authors.lastname: Pasha
authors.affiliation: Department of Discovery Oncology, Genentech, South San Francisco, CA 94080.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Siebel
authors.affiliation: Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208.
authors.forename: Angelica
authors.initials: A
authors.lastname: Costello
authors.affiliation: Translational Lung Biology Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California, Davis, Davis, CA 95616.
authors.forename: Angela
authors.identifier: 0000-0002-1301-4941
authors.initials: A
authors.lastname: Haczku
authors.affiliation: Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208.
authors.forename: Katherine
authors.initials: K
authors.lastname: MacNamara
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liang
authors.affiliation: Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
authors.affiliation: Life Sciences Institute, Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and.|Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Ivan
authors.identifier: 0000-0003-1312-6748
authors.initials: I
authors.lastname: Maillard
authors.affiliation: Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208; yangq@mail.amc.edu.
authors.forename: Qi
authors.identifier: 0000-0002-8365-0986
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D019070:Cell Lineage; D016207:Cytokines / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051880:Receptors, Notch; C539901:Rorc protein, mouse