Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. In this study, we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine interleukin-10 (IL-10) and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors are controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors MMP9 and IL-10 is reduced. We propose that in those states, exacerbated β-cell activity due to increased insulin demand and increased cell death produce high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.

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内源性嘌呤能信号调控人胰岛巨噬细胞的分泌功能

胰岛的内分泌细胞与其微环境相互作用以维持组织稳态。在这种情况下，与局部巨噬细胞的交流尤为重要，但人类胰岛巨噬细胞的稳态功能尚不清楚。在这项研究中，我们表明人类胰岛在血管周围区域含有巨噬细胞，这些区域是抗炎细胞因子白细胞介素 10 (IL-10) 和金属蛋白酶 MMP9 的主要局部来源。这些稳态因子的巨噬细胞产生和分泌受内源性嘌呤能信号控制。在肥胖和糖尿病状态下，嘌呤能受体 MMP9 和 IL-10 的巨噬细胞表达降低。我们建议在这些州，由于胰岛素需求增加和细胞死亡增加导致 β 细胞活性加剧，会产生高水平的 ATP，从而下调嘌呤能受体的表达。巨噬细胞中 ATP 感应的丧失可能会降低其分泌能力。