PIRs mediate innate myeloid cell memory to nonself MHC molecules
PIRs mediate innate myeloid cell memory to nonself MHC molecules
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DOI：
10.1126/science.aax4040
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发表时间：
2020-06-05
期刊：
影响因子：
56.9
通讯作者：
Lakkis, Fadi G.
中科院分区：
文献类型：
--
作者：
Dai, Hehua;Lan, Peixiang;Lakkis, Fadi G.
针对先前发现的抗原的免疫记忆是适应性淋巴细胞的基本特征。然而，尚不清楚先天髓系细胞是否保留了先前抗原刺激的记忆，并在随后的遭遇中对其做出更有力的反应。在这项工作中，我们证明了小鼠单核细胞和巨噬细胞获得了对主要组织相容性复合体I(MHC-I)抗原的特异性记忆，我们发现A型成对免疫球蛋白样受体(PIR-AS)是记忆反应所必需的MHC-I受体。我们证明，在受体中删除PIR-A或阻断PIR-A与供体MHC-I分子的结合会阻断记忆，并减轻肾和心脏移植排斥反应。因此，先天髓系细胞获得同种异体抗原特异性记忆，可作为改善移植结果的靶点。
Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. However, it is unknown whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously on subsequent encounters. In this work, we show that murine monocytes and macrophages acquire memory specific to major histocompatibility complex I (MHC-I) antigens, and we identify A-type paired imrnunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response. We demonstrate that deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocks memory and attenuates kidney and heart allograft rejection. Thus, innate myeloid cells acquire alloantigen-specific memory that can be targeted to improve transplant outcomes.