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 impl...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 specificαchain,theβchain that is shared with IL-2R and the commonγchain.IL-15 is unique in the manner in which it binds and signals through its receptor subunits.IL-15 that is complexed with IL-15Rαbinds to theβγreceptor 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.展开更多
基金funded by NSERC discovery grant to S.R.S.I.D.B.is a recipient of post-doctoral fellowship from FRQS.
文摘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 specificαchain,theβchain that is shared with IL-2R and the commonγchain.IL-15 is unique in the manner in which it binds and signals through its receptor subunits.IL-15 that is complexed with IL-15Rαbinds to theβγreceptor 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.
