title: IFN-α/β receptor signaling promotes regulatory T cell development and function under stress conditions.
abstract: Type I IFNs are a family of cytokines with antiviral and immunomodulatory properties. Although the antiviral effects of IFNs are well characterized, their immunomodulatory properties are less clear. To specifically address the effects of type I IFNs on T regulatory cells (Tregs), we studied mixed bone marrow chimeras between wild-type and IFN-α/β receptor (IFNAR) knockout (KO) mice, and heterozygous female mice expressing a Treg-specific deletion of the IFNAR. In these two models, IFNAR signaling promotes the development of the Treg lineage in the thymus and their survival in the periphery. IFNAR KO Tregs had a higher expression of the proapoptotic gene Bim and higher frequency of active caspase-positive cells. IFNAR KO Tregs from chimeric mice displayed a more naive phenotype, accompanied by lower levels of CD25 and phosphorylated STAT5. Therefore, in Tregs, IFNAR signaling may directly or indirectly affect phosphorylation of STAT5. In mixed chimeras with Scurfy fetal liver, Tregs derived from IFNAR KO bone marrow were unable to control T effector cell activation and tissue inflammation. Under stress conditions or in a competitive environment, IFNAR signaling may be required to maintain Treg homeostasis and function.
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; University Pierre et Marie Curie-Paris 6, 75005 Paris, France;
authors: Amina
authors: A
authors: Metidji
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Sadiye Amcaoglu
authors: SA
authors: Rieder
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Deborah Dacek
authors: DD
authors: Glass
authors: University Pierre et Marie Curie-Paris 6, 75005 Paris, France; INSERM, Centre de Recherche des Cordeliers, 75006 Paris, France; and University Paris Descartes-Paris 5, 75006 Paris, France.
authors: Isabelle
authors: I
authors: Cremer
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: George A
authors: GA
authors: Punkosdy
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; eshevach@niaid.nih.gov.
authors: Ethan M
authors: EM
authors: Shevach
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002678:Chimera; D005260:Female; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013312:Stress, Physiological; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D007370:Interferon Type I; D007376:Interleukin-2; D050799:STAT5 Transcription Factor; D053633:Receptor, Interferon alpha-beta; D011070:Poly I-C