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A novel splice variant of folate receptor 4 predominantly expressed in regulatory T cells

Yi Tian1, Guoqiang Wu2, Jun-Chao Xing2, Jun Tang3, Yi Zhang1, Ze-Min Huang1, Zheng-Cai Jia1, Ren Zhao1, Zhi-Qiang Tian1, Shu-Feng Wang1, Xiao-Ling Chen1, Li Wang1, Yu-Zhang Wu1* and Bing Ni1*

Author Affiliations

1 Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, Peoples Republic China

2 Department of general surgery, the general hospital of ShenYang military area command, ShenYang 110016, Peoples Republic of China

3 Department of Dermatology, the 105th Hospital of PLA, Hefei 230001, Peoples Republic of China

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BMC Immunology 2012, 13:30  doi:10.1186/1471-2172-13-30

Published: 13 June 2012



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.

Folate receptor 4; Variant; Regulatory T cells; Proliferation