Macrophage VISTA restrains inflammatory and antigen-presenting programs during alloimmune tissue injury

T-cell proliferation. Integrative CUT&Tag and RNA-seq analyses further showed that VISTA overexpression was associated with reduced H3K4me3 -associated chromatin remodeling at inflammatory regulatory loci, including TRAF5 and CHDH, together with transcriptional repression of NF-κB-, TNF-, MAPK-, and IL-17-associated inflammatory programs. In vivo F4/80 promoter-directed Vsir restoration shifted intragraft macrophages away from inflammatory polarization, reduced T-cell accumulation, and attenuated early rejection-associated tissue injury. Together, these findings identify VISTA as an intrinsic regulator of macrophage inflammatory programming and point to H3K4me3-associated chromatin remodeling as a regulatory layer linked to VISTA-mediated inflammatory restraint.