Folate Receptor 4 (FR4)

Folates play an important role in protein and nucleic acid biosynthesis and are particularly recognized for their roles in spinal canal and brain development during early pregnancy. FR4 is expressed at high levels on both natural and TGF-b induced Tregs. The majority of CD4+ Tregs express FR4 along with CD25 and FoxP3. FR4 antibodies (e.g. clone 12A5 and TH6) recognize a subtype of the receptor (35kD) for the vitamin folic acid also known as folate receptor d, and folate-binding protein 3. Additionally, there are functional similarities in regulating immune responses between FoxP3 and FR4 expressing CD4+/CD25+ Tregs. CD4+CD25+ FR4hi cells may be used as a functional immunosuppressor Treg population which would be expected to express FoxP3. Accordingly, anti-FR4 antibodies may be useful for cell surface staining of Tregs and easy isolation by FACS or magnetic bead separation while maintaining the cells viability for subsequent down-stream applications.

Key Publication Findings

• FR4 appears to be constitutively expressed in Treg cells at a higher level than other activated or naive T cells

• Not simply a marker for natural Tregs, but functionally essential.