What question did this study set out to answer?

The aim is to understand how the CD74-MIF axis contributes to inflammation during MCMV infection in mice.

February 11, 2026Open Access

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

Key Points

The aim is to understand how the CD74-MIF axis contributes to inflammation during MCMV infection in mice.
Utilized murine models of cytomegalovirus (MCMV) infection to observe inflammatory responses.
Conducted single-cell sequencing to assess CD74 expression in immunocytes.
Measured cytokine levels in vitro following MIF treatment of peripheral blood mononuclear cells.
Investigated the effects of CD74 blockade on cytokine production.
C57BL/6 mice displayed severe inflammation while BALB/c mice had milder symptoms during infection.
Increased CD74 expression and elevated MIF levels were found in C57BL/6 mice.
MIF treatment in vitro led to increased secretion of multiple inflammatory cytokines, including IL-6 and CCL2.
Blocking CD74 partially reduced cytokine production, supporting its role in inflammation.

Abstract

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.

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