IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age
抄録
<jats:title>Abstract</jats:title><jats:p>Decline in immune function and inflammation concomitantly develop with ageing. Here we focus on the impact of this inflammatory environment on T cells, and demonstrate that in contrast to successful tumour elimination in young mice, replenishment of tumour-specific CD4<jats:sup>+</jats:sup> T cells fails to induce tumour regression in aged hosts. The impaired antitumour effect of CD4<jats:sup>+</jats:sup> T cells with their defective Th1 differentiation in an aged environment is restored by interleukin (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired ability of CD4<jats:sup>+</jats:sup> T cells to promote CD8<jats:sup>+</jats:sup> T-cell-dependent tumour elimination in aged mice, which requires IFN-γ. Furthermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1 differentiation. IL-6 also contributes to IL-10 production from CD4<jats:sup>+</jats:sup> T cells in aged mice, causing attenuated responses of CD8<jats:sup>+</jats:sup> T cells. These findings suggest that IL-6 serves as an extrinsic factor counteracting CD4<jats:sup>+</jats:sup> T-cell-mediated immunity against tumour in old age.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 6 (1), 6702-, 2015-04-07
Springer Science and Business Media LLC
