title: The interleukin-15 system suppresses T cell-mediated autoimmunity by regulating negative selection and nT(H)17 cell homeostasis in the thymus.
abstract: The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15(-/-) and Il15ra(-/-) mice spontaneously developed late-onset autoimmune phenotypes. CD4(+) T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15Rα, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4(+) thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity.
authors.affiliation: Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center, Taipei 115, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Mau-Sheng
authors.initials: MS
authors.lastname: Hou
authors.affiliation: Graduate Institute of Life Science, National Defense Medical Center, Taipei 115, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Huang
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan; Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Ching-Cheng
authors.initials: CC
authors.lastname: Yen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yein-Gei
authors.initials: YG
authors.lastname: Lai
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yae-Huei
authors.initials: YH
authors.lastname: Liou
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chih-Kung
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center, Taipei 115, Taiwan; Graduate Institute of Life Science, National Defense Medical Center, Taipei 115, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan. Electronic address: mbfelix@imb.sinica.edu.tw.
authors.forename: Nan-Shih
authors.initials: NS
authors.lastname: Liao
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060966:Clonal Selection, Antigen-Mediated; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000172:deficiency / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011836:Radiation Tolerance / Q000235:genetics; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit
keywords: IL-15; IL-15Rα; Negative selection; Thymus; nT(H)17