1. CISH constrains the tuft–ILC2 circuit to set epithelial and immune tone
- Author
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Kotas, Maya E, Mroz, Nicholas M, Koga, Satoshi, Liang, Hong-Erh, Schroeder, Andrew W, Ricardo-Gonzalez, Roberto R, Schneider, Christoph, and Locksley, Richard M
- Subjects
Digestive Diseases ,Prevention ,Emerging Infectious Diseases ,Underpinning research ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Animals ,Biomarkers ,Cytokines ,Disease Models ,Animal ,Fluorescent Antibody Technique ,Host-Parasite Interactions ,Host-Pathogen Interactions ,Immunity ,Innate ,Immunomodulation ,Lymphocyte Subsets ,Mice ,Mice ,Knockout ,Suppressor of Cytokine Signaling Proteins ,Biological Sciences ,Medical and Health Sciences ,Immunology - Abstract
Innate lymphoid cells (ILCs) are tissue-resident effectors poised to activate rapidly in response to local signals such as cytokines. To preserve homeostasis, ILCs must employ multiple pathways, including tonic suppressive mechanisms, to regulate their primed state and prevent inappropriate activation and immunopathology. Such mechanisms remain incompletely characterized. Here we show that cytokine-inducible SH2-containing protein (CISH), a suppressor of cytokine signaling (SOCS) family member, is highly and constitutively expressed in type 2 innate lymphoid cells (ILC2s). Mice that lack CISH either globally or conditionally in ILC2s show increased ILC2 expansion and activation, in association with reduced expression of genes inhibiting cell-cycle progression. Augmented proliferation and activation of CISH-deficient ILC2s increases basal and inflammation-induced numbers of intestinal tuft cells and accelerates clearance of the model helminth, Nippostrongylus brasiliensis, but compromises innate control of Salmonella typhimurium. Thus, CISH constrains ILC2 activity both tonically and after perturbation, and contributes to the regulation of immunity in mucosal tissue.
- Published
- 2021