Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, United States.
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Elife. 2017 Dec 5;6:e32497. doi: 10.7554/eLife.32497.
Adaptive autoimmunity is restrained by controlling population sizes and pathogenicity of harmful clones, while innate destruction is controlled at effector phase. We report here that deletion of in mouse hematopoietic stem/progenitor cells causes self-destructive innate immunity by massively increasing the population of previously uncharacterized innate myelolymphoblastoid effector cells (IMLECs). Mouse IMLECs are CD3B220NK1.1Ter119 CD11cCD115F4/80Gr-1 CD11b, but surprisingly express high levels of PD-L1. Although they morphologically resemble lymphocytes and actively produce transcripts from Immunoglobulin loci, IMLECs have non-rearranged loci, are phenotypically distinguishable from all known lymphocytes, and have a gene signature that bridges lymphoid and myeloid leukocytes. deletion unleashes differentiation of IMLECs from common myeloid progenitor cells by reducing expression of . Importantly, IMLECs broadly overexpress pattern-recognition receptors and their expansion causes systemic inflammation in response to Toll-like receptor ligands in mice. Our data unveil a novel leukocyte population and an unrecognized role of Raptor/mTORC1 in innate immune tolerance.
适应性自身免疫受到控制种群数量和致病性的有害克隆，而先天破坏在效应阶段受到控制。我们在这里报告，在造血干细胞/祖细胞中缺失导致自我毁灭的先天免疫通过大量增加以前未表征的先天髓样淋巴母细胞效应细胞（IMLECs）的群体。小鼠 IMLECs 是 CD3B220NK1.1Ter119 CD11cCD115F4/80Gr-1 CD11b，但令人惊讶的是，它们表达高水平的 PD-L1。虽然它们在形态上类似于淋巴细胞并积极地从免疫球蛋白基因座产生转录本，但 IMLECs 具有未重排的基因座，与所有已知的淋巴细胞在表型上可区分，并且具有连接淋巴样和髓样白细胞的基因特征。缺失通过降低的表达来释放 IMLECs 从共同髓样祖细胞的分化。重要的是，IMLECs 广泛过表达模式识别受体，其扩增导致小鼠对 Toll 样受体配体的全身性炎症。我们的数据揭示了一种新型白细胞群体和 Raptor/mTORC1 在先天免疫耐受中的未被认识的作用。
