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 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that Tduanyu1842N32 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 Interestingly, engagement of CD3 is sufficient to modulate Tduanyu1842N32 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 Tduanyu1842N32 in polarized T cells under Th1 and Th2 conditions and Tduanyu1842N32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, Tduanyu1842N32 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 Tduanyu1842N32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of Tduanyu1842N32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for Tduanyu1842N32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases.

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