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6 E left panel, males: p = 0.041 and right panel, females p = 0.0001

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Two T1D-associated at-risk variants, rs11203203 and rs80054410, in another regulator of T cell activation and LYP interacting-molecule, UBASH3A , have been shown to increase mRNA expression in human primary CD4+ T cells, thereby reducing IL-2 production by inhibiting NF-B signaling ( UBASH3A variant, has been reported to reduce UBASH3A gene expression in human primary CD4+ T cells, which in contrast increased IL-2 secretion ( UBASH3A deficiency accelerates T1D onset in NOD mice and rats ( PTPN22 and UBASH3A can disrupt critical immune checkpoints, leading to the hyperactivation of T cells and a breakdown of regulatory mechanisms essential for preventing autoimmunity