Supplementary Tables.xlsx

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 two ICs, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are enriched in lesional skin and that reduced PD-L1 expression early after treatment onset predicts 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 a cohort of Sri Lankan CL patients. This finding was confirmed in patients with distinct forms of dermal leishmaniasis in Brazil and India. Furthermore, in our Sri Lankan cohort the abundance of IL-32+ cells and IL-32+CD8+ T cells at treatment onset was prognostic for rate of cure. This study provides a unique spatial perspective on the expression of key ICs in these important skin diseases and a novel route to identify biomarkers of treatment response.人类皮肤利什曼病（cutaneous leishmaniasis, CL）以慢性皮肤病理损害为主要特征。实验与临床数据均表明，免疫检查点（immune checkpoints, ICs）在疾病转归中发挥关键作用，但利什曼病病程中促进免疫检查点表达的细胞与分子微环境仍未明确。本课题组既往研究证实，在斯里兰卡皮肤利什曼病患者体内，吲哚胺2,3-双加氧酶1（indoleamine 2,3-dioxygenase 1, IDO1）与程序性死亡配体1（programmed death-ligand 1, PD-L1）这两种免疫检查点在皮损皮肤中富集；且治疗早期PD-L1表达水平下调可预测锑剂治疗后的治愈率。本研究通过空间细胞互作图谱技术，在斯里兰卡皮肤利什曼病患者队列中，明确表达白细胞介素-32（IL-32）的CD8+记忆性T细胞与调节性T细胞（regulatory T cells）是构成IDO1/PD-L1微环境的核心组分。该发现于巴西与印度的不同类型皮肤利什曼病患者队列中得到验证。此外，在本研究的斯里兰卡患者队列中，治疗初始时IL-32阳性细胞与IL-32阳性CD8+ T细胞的丰度可预测患者的治愈速率。本研究为这类重要皮肤疾病中关键免疫检查点的表达提供了独特的空间视角，同时为鉴定治疗应答生物标志物开辟了全新途径。