02081nas a2200337   4500000000100000008004100001260001200042100000900054700001100063700001000074700001000084700001100094700001000105700000900115700001200124700001000136700001000146700001100156700000900167700001100176700000900187700001000196700001000206700001200216245010000228856005900328300000600387490000600393520133000399022001401729       2022                            d  c01/20221 aMi Z1 aWang Z1 aXue X1 aLiu T1 aWang C1 aSun L1 aYu G1 aZhang Y1 aShi P1 aSun Y1 aYang Y1 aMa S1 aWang Z1 aYu Y1 aLiu J1 aLiu H1 aZhang F00aThe immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing.  uhttps://www.nature.com/articles/s41421-021-00353-3.pdf  a20 v83 a<p>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-DRFBP1 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.</p>
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