Conversely, SEMA6D and its receptor PLXNA4 have been shown to play a critical role in the polarization of macrophages into anti-inflammatory states, and deficiency of SEMA6D in mice results in increased inflammatory cytokine production by peritoneal macrophages as well as predisposition to colitis after intraperitoneal administration of LPS and dextran sodium sulfate (DSS) (24). Here, SEMA6D is linked to colitis.