The CD74-MIF axis contributes to acute uveitic injury by upregulating proinflammatory cytokine secretion in murine cytomegalovirus intracameral infection mouse models.

Murine cytomegalovirus (MCMV) intracameral infection successfully models clinical manifestations resembling CMV-positive Posner-Schlossman Syndrome (PSS). We observed distinct phenotypes in infected C57BL/6 and BALB/c mice: C57BL/6 exhibited severe intraocular inflammation with corneal edema and persistent elevated intraocular pressure (IOP), while BALB/c showed acute IOP spikes with mild uveitis. Single-cell sequencing revealed significant upregulation of CD74 in intraocular CD45+ immunocytes of C57BL/6 mice. CD74, a receptor for macrophage migration inhibitory factor (MIF), is a key regulator of inflammatory pathways. This study found that C57BL/6 with MCMV intracameral infection exhibited increased CD74+ cell counts systemically and intraocularly, alongside elevated intraocular and systemic levels of MIF and various inflammatory cytokines. In vitro, recombinant MIF enhanced cytokine secretion (including IL-6, IL-1β, CCL2, CCL5and CXCL1) in primary peripheral blood mononuclear cells (PBMCs), while CD74 blockade partially inhibited MIF-induced cytokine production. The CD74-MIF interaction is indispensable for cytokine secretion in downstream inflammatory pathways. These findings suggest that the CD74-MIF axis drives ocular inflammation and uveitic damage following MCMV infection in C57BL/6 mice, highlighting its potential as a therapeutic target for immunosuppression in acute uveitis.