Adenosine induces IL-31 secretion by T-helper 2 cells: Implication for the effect of adenosine on atopic dermatitis and its therapeutic strategy.
Adenosine induces IL-31 secretion by T-helper 2 cells: Implication for the effect of adenosine on atopic dermatitis and its therapeutic strategy.
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DOI：
10.1016/j.bbrc.2023.01.038
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发表时间：
2023-01
影响因子：
3.1
通讯作者：
Masaaki Kawano;R. Takagi;Mieko Tokano;S. Matsushita
中科院分区：
文献类型：
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作者：
Masaaki Kawano;R. Takagi;Mieko Tokano;S. Matsushita
白细胞介素（IL）-31是最近发现的一种细胞因子，在瘙痒症的发病机制中具有明确的作用。以前，我们报告说，腺苷上调IL-17 A分泌的辅助性T细胞（Th）17细胞，然而，腺苷对T细胞亚群以外的Th 17的影响仍不清楚。在这份报告中，我们表明，腺苷上调生产的IL-31的分化（CD）4+T细胞的集群。腺苷A2 a受体（A2 aR）激动剂（PSB 0777）也可上调IL-31，而腺苷介导的IL-31产生可被A2 aR拮抗剂（istradefylline）抑制。Th 2相关细胞因子（IL-4、IL-10和IL-13）由CD 4 +T细胞产生显示出相同的趋势。免疫亚群分析显示，腺苷上调CD 4+趋化因子受体3 highT细胞分泌IL-31，Th 2细胞从幼稚的CD 4 +T细胞分化。对患有特应性皮炎的小鼠施用istradefylline抑制了症状，表明A2 aR拮抗剂是炎性皮炎的有效治疗。综上所述，结果表明腺苷上调皮肤中效应T细胞分泌Th 2相关细胞因子，从而引发特应性皮炎和相关瘙痒。
Interleukin (IL)-31 is a recently-identified cytokine with a well-defined role in the pathogenesis of pruritus. Previously, we reported that adenosine upregulates IL-17A secretion by T-helper (Th)17 cells; however, the effect of adenosine on T cell subsets other than Th17 remains unclear. In this report, we show that adenosine upregulated production of IL-31 by cluster of differentiation (CD)4+T cells. IL-31 was also upregulated by administration of an adenosine A2a receptor (A2aR) agonist (PSB0777), and adenosine-mediated IL-31 production was inhibited by an A2aR antagonist (istradefylline). Production of Th2-related cytokines (IL-4, IL-10, and IL-13) by CD4+T cells showed the same tendency. Immune subset analyses revealed that adenosine upregulated IL-31 secretion by CD4+chemokine receptor 3highT cells, and that Th2 cells differentiated from naïve CD4+T cells. Administration of istradefylline to mice with atopic dermatitis suppressed the symptoms, suggesting that A2aR antagonists are an effective treatment for inflammatory dermatitis. Taken together, the results indicate that adenosine upregulates secretion of Th2-related cytokines by effector T cells in the skin, thereby triggering atopic dermatitis and associated pruritus.