银屑病关节炎中 白介素15通过NKG2D,cPLA2介导NK细胞杀伤作用
译者:李变变 校对者:梁美娥 审核者:张莉芸
Interleukin Primes Natural Killer Cells to Kill via NKG2D and cPLA2 and This PathwayIs Active in Psoriatic Arthritis
Abstract:NK cells are large granular lymphocytes that form a critical component of the innate immune system, whose functions include the killing of cells expressing stress-induced molecules. It is increasingly accepted that despite being considered prototypical effector cells, NK cells require signals to reach their full cytotoxic potential. We previously showed that IL-15 is capable of arming CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2-dependent process. As NK cells also express NKG2D, we wanted to investigate whether this pathway functioned in an analogous manner and if resting NK cells could be primed to the effector phase by IL-15. Furthermore, to establish relevance to human disease we studied a possible role for this pathway in the pathogenesis of psoriatic arthritis, since there are aspects of this disease that suggest a potential effector role for the innate immune system. We found that PsA patients had upregulated IL-15 and MIC in their affected synovial tissues, and that this unique inflammatory environment enabled NK cell activation and killing via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint NK cells from blood NK cells by incubating them with IL-15. Altogether, these findings suggest a destructive role for NK cells when activated by environmental stress signals during the pathogenesis of PsA and demonstrate that IL-15 is capable of priming resting NK cells in tissues to the effector phase.
NK细胞是一种大分子,颗粒状淋巴细胞,参与形成固有免疫系统,其功能包括杀伤表达应激诱导分子的细胞。尽管NK细胞被认为是典型的效应细胞,但其仍需要信号来实现细胞毒的潜能。我们过去认为白介素15能瞄准CD8效应T细胞,通过NKG2D(存在于一个依赖cPLA2的过程)来杀死TCR。由于NK细胞也能表达NKG2D,我们也想去调查NK细胞是否存在相似的途径,休眠中的NK细胞能否被白介素15激活至效应阶段。进一步说,为建立与人类疾病的相关性,我们从银屑病关节炎的发病原理出发,原因是在银屑病关节炎中NK细胞可能是一潜在的固有免疫效应器。我们发现银屑病关节炎病人的滑膜组织中存在白介素15,MIC。这一独特的炎性环境通过NKG2D,cPLA2激活NK细胞发挥杀伤作用。我们利用白介素15复制来自血液NK细胞的关节NK细胞表型。这些发现暗示:在银屑病关节炎的发病中,环境中的应急信号激活NK细胞,IL-15能促使组织中休眠的NK细胞达到效应阶段。