Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion.
Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion.
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DOI：
10.1371/journal.pone.0048574
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hirashima M
中科院分区：
文献类型：
--
作者：
Oomizu S;Arikawa T;Niki T;Kadowaki T;Ueno M;Nishi N;Yamauchi A;Hattori T;Masaki T;Hirashima M
Galectin-9(Galectin-9，Galectin-9)是一种与β-半乳糖苷结合的哺乳动物凝集素，在体内外通过减少促炎性IL-17产生的Th细胞(Th17)和增加抗炎的Foxp3+调节性T细胞(Treg)来调节免疫反应。Gal-9的这些功能被认为是通过与细胞表面的受体分子结合而发挥的。然而，Gal-9缺乏分泌信号肽，主要位于细胞质中，这引发了关于体内哪些细胞如何以及哪些细胞分泌Gal-9的问题。由于Gal-9的表达与其分泌并不一定相关，体内的Gal-9分泌细胞一直难以捉摸。我们在此报道，细胞表面表达Gal-9的CD4T细胞(Gal-9+Th细胞)在T细胞受体(TCR)刺激下分泌Gal-9，而其他CD4T细胞不分泌Gal-9，尽管它们在细胞内表达等量的Gal-9。Gal-9+Th细胞表达白介素10和转化生长因子β，但不表达Foxp3。在共培养实验中，Gal-9+Th细胞调节Th17/Treg的方式与外源性Gal-9相似，在此过程中，Gal-9+Th细胞对Gal-9拮抗剂敏感，但对IL-10和转化生长因子-β拮抗剂不敏感。对人类Gal-9+Th细胞的进一步阐明表明这些细胞在进化过程中具有保守的作用，并暗示这些细胞可能用于诊断或治疗免疫性疾病。
Galectin-9 (Gal-9), a β-galactoside binding mammalian lectin, regulates immune responses by reducing pro-inflammatory IL-17-producing Th cells (Th17) and increasing anti-inflammatory Foxp3+ regulatory T cells (Treg) in vitro and in vivo. These functions of Gal-9 are thought to be exerted by binding to receptor molecules on the cell surface. However, Gal-9 lacks a signal peptide for secretion and is predominantly located in the cytoplasm, which raises questions regarding how and which cells secrete Gal-9 in vivo. Since Gal-9 expression does not necessarily correlate with its secretion, Gal-9-secreting cells in vivo have been elusive. We report here that CD4 T cells expressing Gal-9 on the cell surface (Gal-9+ Th cells) secrete Gal-9 upon T cell receptor (TCR) stimulation, but other CD4 T cells do not, although they express an equivalent amount of intracellular Gal-9. Gal-9+ Th cells expressed interleukin (IL)-10 and transforming growth factor (TGF)-β but did not express Foxp3. In a co-culture experiment, Gal-9+ Th cells regulated Th17/Treg development in a manner similar to that by exogenous Gal-9, during which the regulation by Gal-9+ Th cells was shown to be sensitive to a Gal-9 antagonist but insensitive to IL-10 and TGF-β blockades. Further elucidation of Gal-9+ Th cells in humans indicates a conserved role of these cells through evolution and implies the possible utility of these cells for diagnosis or treatment of immunological diseases.
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