CD74 is a functional MIF receptor on activated CD4⁺ T cells

Area of Science:

• Immunology
• Cell Biology
• Molecular Medicine

Background:

• CD74 traditionally functions in MHC II antigen presentation.
• CD74 is a high-affinity receptor for macrophage migration inhibitory factor (MIF).
• The role of CD74 in T cells and its interaction with MIF is poorly understood.

Purpose of the Study:

• To investigate CD74 expression and MIF receptor regulation during human CD4+ T cell activation.
• To determine the functional relevance of CD74 in MIF-induced T cell migration and function.
• To explore the link between CD74 expression and COVID-19 disease severity.

Main Methods:

• Flow cytometry for receptor profiling of T cells.
• Western blot, immunohistochemistry, and analysis of omics data for CD74 expression.
• 3D-matrix live cell imaging and receptor inhibitors to study T cell migration.
• Proximity ligation assay to visualize receptor heterocomplexes.
• Analysis of T cell samples from COVID-19 patients.

Main Results:

• Resting CD4+ T cells express intracellular CD74 and surface CXCR4; activated T cells upregulate cell surface CD74.
• CD74 and CXCR4 are causally involved in MIF-induced CD4+ T cell migration.
• MIF treatment leads to diminished CD74/CXCR4 heterocomplexes, suggesting internalization.
• Increased CD74 surface expression on CD4+ and CD8+ T cells correlates with severe COVID-19.

Conclusions:

• CD74 is a novel, functional MIF receptor on activated human T cells.
• CD74 acts as an MHC II-independent activation marker for CD4+ T cells.
• The MIF-T cell receptor network is dynamically regulated during T cell activation and is relevant in COVID-19 pathogenesis.