Collectively, our findings infer a mechanism in which peripherally circulating factors induced by stroke trigger ADAM17-dependant CD163 shedding by monocytes, driving an increase in sCD163 levels which act to suppress peripheral lymphocyte activity; this mechanism likely serves as a means of maintaining self-tolerance as the blood brain barrier becomes disrupted and peripheral lymphoid populations become exposed to activated innate antigen presenting cells loaded with unfamiliar neural antigens (Fig. 6). This evidence concerns the gene CD163 and stroke disorder.