CD4 and skin disorder: Summarizing the observations in murine and human studies [32,33,34,35,36], blockade of the CD137-CD137L co-stimulation system by deleting the CD137 gene leads to more severe SLE phenotypes including immune-mediated glomerulonephritis, profound lymphadenopathy and splenomegaly and dermatitis as a result of increased autoreactive pathogenic CD4+ T cells and functional B220+CD5- B cells, leading to subsequent autoantibody production [37,38].