ITGAM and systemic lupus erythematosus: Interestingly, cells from donors carrying ITGAM variants showed increased transcript levels of IFNB and IRF7 and significantly reduced protein levels of FOXO3 in the nucleus (14), suggesting a key mechanism behind increased IFN I levels in SLE and LN patients—that the ITGAM variants likely reduce a CD11b-dependent tonic suppression of TLR signaling in cells, due to a failure of the mutant CD11b integrin in maintaining nuclear FOXO3 levels, resulting in reduced suppression of IRF7 (56) and increased IFN-I (14).