调节四跨膜蛋白32（TSPAN32）在T细胞介导的免疫反应和多发性硬化症中的表达。,International Journal of Molecular Sciences

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调节四跨膜蛋白32（TSPAN32）在T细胞介导的免疫反应和多发性硬化症中的表达。
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2019-09-04 , DOI: 10.3390/ijms20184323
Salvo Danilo Lombardo ₁ , Emanuela Mazzon ₂ , Maria Sofia Basile ₁ , Giorgia Campo ₁ , Federica Corsico ₁ , Mario Presti ₁ , Placido Bramanti ₂ , Katia Mangano ₁ , Maria Cristina Petralia ₂ , Ferdinando Nicoletti ₁ , Paolo Fagone ₁

Affiliation

四跨膜蛋白是一种保守的蛋白质家族，涉及许多生物学过程，包括细胞-细胞相互作用，繁殖力，癌症转移和免疫反应。先前已证明，TSPAN32基因敲除小鼠的造血和B细胞反应正常，但T细胞过度增殖。在这里，我们显示与骨髓细胞相比，TSPAN32在淋巴谱系中的表达水平更高。通过抗CD3 / CD28的T辅助细胞的体外激活与TSPAN32的显着下调有关。有趣的是，CD3的参与足以调节TSPAN32的表达，并且通过与抗CD28（而非抗CTLA4，-ICOS或-PD1）共同刺激来增强其作用。因此，我们测量了在Th1和Th2条件下极化T细胞中TSPAN32的转录组水平，与未刺激的细胞相比，TSPAN32的结果显着降低。另一方面，在Treg细胞中，TSPAN32在激活后发生了微小变化。最终将体外数据转化为多发性硬化症（MS）。髓鞘少突胶质糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE）小鼠的致脑T细胞显示TSPAN32水平明显降低，CD9，CD53，CD82和CD151水平升高。类似地，与健康供体相比，MS患者的体外活化循环CD4 T细胞显示出较低的TSPAN32水平。总体，

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Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis.

Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell-cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that TSPAN32 is expressed at higher levels in the lymphoid lineage as compared to myeloid cells. In vitro activation of T helper cells via anti-CD3/CD28 is associated with a significant downregulation of TSPAN32. Interestingly, engagement of CD3 is sufficient to modulate TSPAN32 expression, and its effect is potentiated by costimulation with anti-CD28, but not anti-CTLA4, -ICOS nor -PD1. Accordingly, we measured the transcriptomic levels of TSPAN32 in polarized T cells under Th1 and Th2 conditions and TSPAN32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, TSPAN32 underwent minor changes upon activation. The in vitro data were finally translated into the context of multiple sclerosis (MS). Encephalitogenic T cells from Myelin Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis (EAE) mice showed significantly lower levels of TSPAN32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of TSPAN32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for TSPAN32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases.

更新日期：2019-11-01

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