IL-32 producing CD8 + memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions
IL-32 producing CD8 + memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions
复制标题
产生 IL-32 的 CD8 记忆 T 细胞和 Tregs 定义了人皮肤利什曼病皮肤病变中的 IDO1 / PD-L1 生态位
DOI：
10.1101/2024.01.02.23300281
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Dey N
中科院分区：
文献类型：
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作者：
Dey N
人类皮肤利什曼病（CL）的特征是慢性皮肤病理学。实验和临床数据表明，免疫检查点（IC）在疾病的结果中起着至关重要的作用，但利什曼病期间促进IC表达的细胞和分子生态位是不明确的。我们之前的研究表明，在斯里兰卡CL患者中，吲哚胺2，3-双加氧酶1（IDO 1）和程序性死亡配体1（PD-L1）在病变皮肤中富集，治疗开始后早期PD-L1表达降低可预测锑治疗后的治愈率。在这里，我们使用空间细胞相互作用映射来识别IL-32表达的CD 8+记忆细胞和调节性T细胞作为斯里兰卡CL患者以及巴西和印度不同形式的皮肤利什曼病患者中IDO 1/ PD-L1生态位的关键组成部分。此外，治疗开始时IL-32+细胞和IL-32+ CD 8 +T细胞的丰度是斯里兰卡患者治愈率的预后指标。这项研究为CL期间IC表达的机制提供了独特的空间视角，并为识别治疗反应的其他生物标志物提供了新途径。
Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome but the cellular and molecular niches that facilitate IC expression during leishmaniasis are ill-defined. We previously showed that in Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are enriched in lesion skin and that reduced PD-L1 expression early after treatment onset predicted cure rate following antimonial therapy. Here, we use spatial cell interaction mapping to identify IL-32-expressing CD8+memory cells and regulatory T cells as key components of the IDO1 / PD-L1 niche in Sri Lankan CL patients and in patients with distinct forms of dermal leishmaniasis in Brazil and India. Furthermore, the abundance of IL-32+cells and IL-32+CD8+T cells at treatment onset was prognostic for rate of cure in Sri Lankan patients. This study provides a unique spatial perspective on the mechanisms underpinning IC expression during CL and a novel route to identify additional biomarkers of treatment response.Graphical Abstract