Although we used the knockout systems to identify the role of STAT4 in autoimmune responses and autoimmunity development in autoimmune- or SLE-prone mouse models, it is possible that overexpression of STAT4 in SLE patients may take on novel functions or may function in concert with other genetic predispositions, such as IRF5 variants, to contribute to SLE disease (47). Here, IRF5 is linked to systemic lupus erythematosus.