It has also been demonstrated that the TCR–CD3 complex that recognizes (auto-)antigens and mediates T cell activation is ‘rewired’ in SLE T lymphocytes, contributing to an amplified T cell activation in SLE [53]. Evidence suggests the involvement of CREMα in the ‘skewed’ TCR–CD3 composition in SLE T cells, which sees replacement of the normal TCR ζ chain by the ‘common’ FcRγ chain. CREMα trans-represses the TCR ζ chain promoter and mediates chromatin remodeling through histone deacetylation, contributing to defective ζ chain expression and its replacement by the common FcRγ chain in the TCR–CD3 complex. This has tremendous significance for the subsequent signaling events because FcRγ-mediated downstream signaling is far more potent than that mediated through the ζ chain.
