Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-β production
Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-β production
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DOI：
10.1016/j.bbrc.2011.10.119
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发表时间：
2011-11-25
影响因子：
3.1
通讯作者：
Yasukawa, Masaki
中科院分区：
文献类型：
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作者：
Hasegawa, Hitoshi;Lei, Jin;Yasukawa, Masaki
自然产生的CD4(+)CD25（+）调节性T细胞（nTregs）在维持自身耐受性和免疫稳态中起关键作用。为了深入了解nTregs在病理和生理免疫反应中的作用机制，分析调节nTregs维持和功能的生物活性分子是很重要的。从生物活性脂类库中，我们获得了溶血磷脂酰胆碱（LPC）分子，与dmso处理的nTregs（对照）相比，LPC分子显著增强了人类nTregs的Foxp3表达和抑制功能。lpc处理的nTregs中tgf - β 1 mRNA和蛋白的表达水平显著高于对照nTregs。经抗tgf - β 1抗体治疗后，lpc处理的nTregs的Foxp3表达增加和抑制特性恢复到对照nTregs的水平。这些发现表明，LPC通过nTregs自身产生的tgf - β 1增强了Foxp3的表达和nTregs的抑制功能。G2A和GPR4的实验敲低表明，lpc诱导的nTregs中tgf - β 1的表达是由G2A信号传导引起的，与GPR4无关。此外，尽管LPC通过G2A激活了包括ERK1/2、p38 MAPK和JNK在内的MAPK，但JNK是LPC诱导的ntreg中tgf - β 1表达的主要因素。LPC是一种在血液循环中含量丰富的生物活性溶脂。因此，LPC可能有助于体内人类nTregs的维持和功能。(C) 2011爱思唯尔公司版权所有。
Naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) play a pivotal role in the maintenance of self-tolerance and immune homeostasis. To gain insight into the mechanism of action of nTregs in pathological and physiological immune responses, it is important to analyze bioactive molecules that modulate the maintenance and function of nTregs. From a library of bioactive lipids, we obtained lysophosphatidylcholine (LPC) as a molecule that enhanced the Foxp3 expression and suppressive function of human nTregs significantly in comparison with those of DMSO-treated nTregs (control). The expression levels of TGF-beta 1 mRNA and protein in LPC-treated nTregs were significantly higher than those in control nTregs. After treatment with anti-TGF-beta 1 antibody, the increases in Foxp3 expression and the suppressive properties of LPC-treated nTregs returned to the levels observed in control nTregs. These findings indicate that LPC enhances Foxp3 expression and the suppressive function of nTregs through TGF-beta 1 produced by nTregs themselves. Experimental knockdown of G2A and GPR4 showed that this LPC-induced TGF-beta 1 expression in nTregs was due to G2A signaling, and did not involve GPR4. Moreover, JNK was a major contributor to LPC-induced TGF-beta 1 expression in nTregs, although LPC activated MAPKs including ERK1/2, p38 MAPK, and JNK via G2A. LPC is a bioactive lysolipid highly abundant in the circulation. Therefore, LPC may contribute to the maintenance and function of human nTregs in vivo. (C) 2011 Elsevier Inc. All rights reserved.