Thrombospondin-1（TSP1）是一种在健康状态下表达较少但在疾病和年龄增长时增加的分泌蛋白质。TSP1与细胞膜受体CD47结合，CD47又与信号调节蛋白α（SIRPα）相互作用，后者创建了免疫激活检查点。使用阻断检查点分子治疗癌症的个体会发展出胰岛素依赖性糖尿病。关于这一点，CD47阻断抗体和SIRPα融合蛋白正在进行临床试验。我们表征了人胰岛和胰腺中TSP1、CD47和SIRPα的分子标记。获得了非糖尿病个体的新鲜胰岛和胰腺组织。使用单细胞mRNA测序、免疫荧光显微镜、Western blot和流式细胞术确定THBS1，CD47和SIRPA的表达。将胰岛暴露于与糖尿病相关的炎症细胞因子，以确定蛋白质表达的变化。所有胰岛细胞类型中均表达CD47 mRNA。THBS1 mRNA主要限于内皮和间充质细胞，而SIRPA mRNA主要在巨噬细胞中发现。免疫荧光染色显示β细胞表达CD47蛋白，并存在于外分泌胰腺中。TSP1和SIRPα蛋白未在胰岛或外分泌胰腺中发现。Western blot和流式细胞术证实免疫荧光表达模式。重要的是，人胰岛产生了大量分泌的TSP1。人胰腺外分泌和内分泌组织表达CD47，而新鲜胰岛在基线和炎症情况下显示细胞表面CD47和分泌的TSP1。这些发现表明与TSP1-CD47-SIRPα相交的药物对胰岛的影响是出乎意料的。

Thrombospondin-1 (TSP1) is a secreted protein minimally expressed in health but increased in disease and age. TSP1 binds to the cell membrane receptor CD47, which itself engages signal regulatory protein α (SIRPα) and the latter creates a checkpoint for immune activation. Individuals with cancer administered checkpoint blocking molecules developed insulin-dependent diabetes. Relevant to this, CD47 blocking antibodies and SIRPα fusion proteins are in clinical trials. We characterized the molecular signature of TSP1, CD47, and SIRPα in human islets and pancreata.Fresh islets and pancreatic tissue from non-diabetic individuals were obtained. The expression of THBS1, CD47, and SIRPA was determined using single-cell mRNA sequencing, immunofluorescence microscopy, Western blot, and flow cytometry. Islets were exposed to diabetes-affiliated inflammatory cytokines and changes in protein expression determined.CD47 mRNA was expressed in all islet cell types. THBS1 mRNA was restricted primarily to endothelial and mesenchymal cells, while SIRPA mRNA was found mostly in macrophages. Immunofluorescence staining showed CD47 protein expressed by beta cells and present in the exocrine pancreas. TSP1 and SIRPα proteins were not seen in islets or the exocrine pancreas. Western blot and flow cytometry confirmed immunofluorescent expression patterns. Importantly, human islets produced substantial quantities of secreted TSP1.Human pancreatic exocrine and endocrine tissue expressed CD47 whereas fresh islets displayed cell surface CD47 and secreted TSP1 at baseline and in inflammation. These findings suggest unexpected effects on islets from agents that intersect TSP1-CD47-SIRPα.