The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing.
The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing.
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单细胞 RNA 测序揭示肿瘤性麻风病的免疫抑制景观
DOI：
10.1038/s41421-021-00353-3
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发表时间：
2022-01-11
期刊：
影响因子：
33.5
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Mi Z;Wang Z;Xue X;Liu T;Wang C;Sun L;Yu G;Zhang Y;Shi P;Sun Y;Yang Y;Ma S;Wang Z;Yu Y;Liu J;Liu H;Zhang F
麻风病 (L-LEP) 是由麻风分枝杆菌主要在巨噬细胞中大量增殖引起的，是研究细胞内细菌逃避或调节宿主免疫反应的分子机制的理想疾病模型。在这里，我们对 L-LEP 患者和健康对照的皮肤活检和外周血单核细胞 (PBMC) 进行了单细胞 RNA 测序。在 L-LEP 病变中，我们发现在 LIPA 高表达水平的巨噬细胞亚群中，APOE 表达显着上调，与主要组织相容性复合体 II 基因 HLA-DQB2 和 MIF 呈负相关，MIF 编码促炎和抗微生物细胞因子。 L-LEP 病灶中 TIGIT 和 LAG3 高表达为 CD8+ T 细胞耗竭的表现。此外，在 L-LEP 病变中观察到抑制性免疫受体介导的皮肤免疫细胞之间的串扰显着增强。对于PBMC，HLA-DRhighFBP1high单核细胞亚群中APOE的高表达水平和调节性T细胞的扩增被发现与L-LEP相关。这些发现揭示了 L-LEP 患者的主要抑制状况，为干预引起持续感染的细胞内细菌提供了潜在的靶点。
Lepromatous leprosy (L-LEP), caused by the massive proliferation of Mycobacterium leprae primarily in macrophages, is an ideal disease model for investigating the molecular mechanism of intracellular bacteria evading or modulating host immune response. Here, we performed single-cell RNA sequencing of both skin biopsies and peripheral blood mononuclear cells (PBMCs) of L-LEP patients and healthy controls. In L-LEP lesions, we revealed remarkable upregulation of APOE expression that showed a negative correlation with the major histocompatibility complex II gene HLA-DQB2 and MIF, which encodes a pro-inflammatory and anti-microbial cytokine, in the subset of macrophages exhibiting a high expression level of LIPA. The exhaustion of CD8+ T cells featured by the high expression of TIGIT and LAG3 in L-LEP lesions was demonstrated. Moreover, remarkable enhancement of inhibitory immune receptors mediated crosstalk between skin immune cells was observed in L-LEP lesions. For PBMCs, a high expression level of APOE in the HLA-DRhighFBP1high monocyte subset and the expansion of regulatory T cells were found to be associated with L-LEP. These findings revealed the primary suppressive landscape in the L-LEP patients, providing potential targets for the intervention of intracellular bacteria caused persistent infections.
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影响因子：
8.1
作者：
Fonseca AB;Simon MD;Cazzaniga RA;de Moura TR;de Almeida RP;Duthie MS;Reed SG;de Jesus AR
通讯作者：
de Jesus AR
影响因子：
--
作者：
Loureiro J;Ploegh HL
通讯作者：
Ploegh HL
影响因子：
32.4
作者：
Hughes TK;Wadsworth MH 2nd;Gierahn TM;Do T;Weiss D;Andrade PR;Ma F;de Andrade Silva BJ;Shao S;Tsoi LC;Ordovas-Montanes J;Gudjonsson JE;Modlin RL;Love JC;Shalek AK
通讯作者：
Shalek AK
影响因子：
4.6
作者：
Ackermann, Christin;Smits, Maike;Wiesch, Julian Schulze Zur
通讯作者：
Wiesch, Julian Schulze Zur
影响因子：
5.4
作者：
Holtzman, David M.;Herz, Joachim;Bu, Guojun
通讯作者：
Bu, Guojun