Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS-940, F-75010 Paris, France.
Hum Immunol. 2013 Dec;74(12):1536-41. doi: 10.1016/j.humimm.2013.08.281. Epub 2013 Aug 29.
A soluble isoform of MHC class I chain-related molecule A (soluble MICA), generated by proteolytic shedding from the membrane-bound MICA of various tumor cells, has been shown to downregulate both the expression of natural killer group 2-member D receptor and the cytotoxic function of effectors cells and was postulated as a mechanism for tumor immune evasion. Its effect on the expression of cytokines by the effector cells remained unexplored. Here we demonstrate that the sMICA molecules upregulate interferon gamma expression by interleukin-12/interleukin-18-activated CD3(-)CD56(+) natural killer cells, witnessing the pro-inflammatory effect of soluble MICA. Overall, these data are in line with our previous observations that the raised serum levels of soluble MICA, following allogeneic hematopoietic stem cell transplantation, confer susceptibility to and the presence of pre-transplantation anti-MICA antibodies in the patient's serum confer protection against chronic graft versus host disease.
MHC Ⅰ类链相关分子 A 的可溶型异构体（sMICA）由各种肿瘤细胞表面结合型 MICA 通过蛋白水解脱落产生，已被证实可下调自然杀伤细胞组 2 成员 D 受体的表达和效应细胞的细胞毒性功能，被认为是肿瘤免疫逃逸的一种机制。但其对效应细胞细胞因子表达的影响尚不清楚。本文中我们证明 sMICA 分子可上调白细胞介素 12/18 激活的 CD3(-)CD56(+)自然杀伤细胞中干扰素 γ的表达，表明可溶性 MICA 具有促炎作用。总体而言，这些数据与我们之前的观察结果一致，即同种异体造血干细胞移植后血清可溶性 MICA 水平升高，使患者易患慢性移植物抗宿主病，而移植前患者血清中存在抗-MICA 抗体则可对此起到保护作用。
