title: Trans-presentation of interleukin-15 by interleukin-15 receptor alpha is dispensable for the pathogenesis of autoimmune type 1 diabetes.
abstract: Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is required for the survival and activation of memory CD8+T cells, natural killer (NK) cells, innate lymphoid cells, macrophages and dendritic cells. IL-15 is implicated in the pathogenesis of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis and autoimmune type 1 diabetes (T1D). IL-15 receptor (IL-15R) consists of a specific α chain, the β chain that is shared with IL-2R and the common γ chain. IL-15 is unique in the manner in which it binds and signals through its receptor subunits. IL-15 that is complexed with IL-15Rα binds to the βγ receptor complex present on the responding cell to mediate its biological effects through a process referred to as trans-presentation. The trans-presented IL-15 is essential to mediate the biological effects on T lymphocytes and NK cells. Here we show that IL-15, but not IL-15Rα, is required for the development of spontaneous and virus-induced T1D, viral clearance and for antigen cross-presentation to CD8+T lymphocytes. Our findings provide insight into the complexities of IL-15 signalling in the initiation and maintenance of CD8+T cell-mediated immune responses.
authors: Immunology Division, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Diwakar
authors: D
authors: Bobbala
authors: Immunology Division, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Marian
authors: M
authors: Mayhue
authors: Department of Microbiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.|Centre de rechercheclinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Alfredo
authors: A
authors: Menendez
authors: Immunology Division, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada.|Centre de rechercheclinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Subburaj
authors: S
authors: Ilangumaran
authors: Immunology Division, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada.|Centre de rechercheclinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Sheela
authors: S
authors: Ramanathan
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism*; D019409:Interleukin-15 / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D051381:Rats
chemical_list: D000956:Antigens, Viral; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit