Institute of Immunology, PLA, Third Military Medical University, Chongqing, Peoples Republic China.
BMC Immunol. 2012 Jun 13;13:30. doi: 10.1186/1471-2172-13-30.
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.
调节性 T 细胞(Tregs)对于维持免疫耐受和免疫稳态至关重要。叶酸受体 4(FR4)在转化生长因子-β(TGF-β)诱导的 Tregs 和天然 Tregs 中高表达。此外,抗体介导的 FR4 靶向足以介导 Treg 耗竭。
在这项研究中,我们描述了一种新型的 FR4 转录变体 FR4D3,其中外显子 3 缺失。FR4D3 的 mRNA 编码一个缺失 189bp 的 FR4 变体。FR4D3 主要在 CD4+CD25+Treg 细胞中表达。体外过表达 FR4D3 可刺激 CD4+CD25+Treg 细胞增殖,这可能调节这些细胞结合和摄取叶酸的能力。
我们的结果表明,高水平的 FR4D3 可能对支持 Treg 细胞的大量增殖能力至关重要。