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Regulatory T cells (Tregs) are required for proper maintenance of immunological self-tolerance and immune homeostasis. Folate receptor 4 (FR4) is expressed at high levels in transforming growth factor-beta (TGF-β)-induced Tregs and natural Tregs. Moreover, antibody-mediated targeting of FR4 is sufficient to mediate Treg depletion. In this study, we describe a novel FR4 transcript variant, FR4D3, in which exon 3 is deleted. The mRNA of FR4D3 encodes a FR4 variant truncated by 189 bp. FR4D3 was found to be predominantly expressed in CD4(+)CD25(+) Treg cells. Overexpression of FR4D3 in CD4(+)CD25(+) Treg cells in vitro stimulated proliferation, which may modulate the ability of these cells to bind and incorporate folic acid. Our results suggested that high levels of FR4D3 may be critical to support the substantial proliferative capacity of Treg cells.

Citation

Yi Tian, Guoqiang Wu, Jun-Chao Xing, Jun Tang, Yi Zhang, Ze-Min Huang, Zheng-Cai Jia, Ren Zhao, Zhi-Qiang Tian, Shu-Feng Wang, Xiao-Ling Chen, Li Wang, Yu-Zhang Wu, Bing Ni. A novel splice variant of folate receptor 4 predominantly expressed in regulatory T cells. BMC immunology. 2012 Jun 13;13:30

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PMID: 22694797

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