Folate receptor β performs an immune checkpoint function in activated macrophages.

Area of Science:

• Immunology
• Cancer Biology
• Molecular Biology

Background:

• Monocytes and macrophages express folate receptor beta (FRβ), a unique immune cell marker.
• FRβ binding to folate is regulated by immunosuppressive cytokines, suggesting a potential immune function.

Purpose of the Study:

• To investigate the immune-related function of FRβ.
• To determine FRβ's role in autoimmune diseases and tumor immunity.

Main Methods:

• Comparison of wild-type (WT) and FRβ knockout (KO) mice.
• Analysis of autoimmune symptoms, tumor growth, and immune cell populations in tumors.
• Gene expression analysis of bone marrow-derived macrophages.
• In vitro studies of macrophage-T cell interaction.

Main Results:

• FRβ KO mice exhibit autoimmune symptoms (alopecia, dermatitis) and slower tumor growth.
• KO tumors show increased CD69+ T cells and decreased PD1+ T cells and PD-L1+ myeloid cells.
• FRβ deletion upregulates pro-inflammatory genes and downregulates anti-inflammatory genes in macrophages.
• FRβ blockade or deletion impairs macrophage-mediated suppression of T cell activation.

Conclusions:

• FRβ functions as an immune checkpoint regulating myeloid cell immunologic properties.
• FRβ plays an immunosuppressive role in tumor immunity.
• FRβ may have a similar immunosuppressive function in human cancers, correlating inversely with survival.