IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development.
IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development.
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DOI：
10.1038/s41598-021-84624-9
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发表时间：
2021-03-04
影响因子：
4.6
通讯作者：
Yoshimoto T
中科院分区：
文献类型：
--
作者：
Hasegawa H;Mizoguchi I;Orii N;Inoue S;Katahira Y;Yoneto T;Xu M;Miyazaki T;Yoshimoto T
在各种细胞因子中，白细胞介素（IL）-12家族细胞因子具有非常独特的特征，因为它们由两个不同的亚基组成，并且这些亚基彼此共享。 IL-23是IL-12家族细胞因子之一，由p19和p40亚基组成，主要由抗原呈递细胞产生，在致病性辅助CD4+ T (Th)17细胞的扩增和维持中发挥关键作用。由于我们最初发现p19分泌于活化的CD4+T细胞的培养上清液中，因此我们进一步研究了p19的作用。 p19被发现与CD5抗原样（CD5L）相关，CD5L是Th17致病性的抑制因子，并且在非致病性Th17细胞中高表达，形成复合p19/CD5L。该 p19/CD5L 显示可激活 STAT5 并增强分化为产生粒细胞巨噬细胞集落刺激因子 (GM-CSF) 的 CD4+ T 细胞。 CD4+ T 细胞特异性条件性 p19 缺陷小鼠和完全 CD5L 缺陷小鼠均表现出实验性自身免疫性脑脊髓炎 (EAE) 显着减轻，且 GM-CSF+CD4+ T 细胞频率降低。在EAE病程中，p19/CD5L（而非CD5L）的血清水平与临床症状高度相关。因此，复合 p19/CD5L 是一种可能的新型异二聚体细胞因子，通过 GM-CSF 上调促进 EAE 发展。
Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4+ T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4+ T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4+ T cells. Both CD4+ T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSF+CD4+ T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation.
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影响因子：
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