GPR109A表达在骨髓胸膜上皮细胞上影响胸膜Treg发育
Duan Ni1,2, Jian Tan1,2, Remy Robert3
1Charles Perkins Centre, The University of Sydney, The University of Sydney, New South Wales, Australia.
European journal of immunology
|August 18, 2023
概括
G蛋白结合受体109A (GPR109A) 调节胸膜调节性T细胞 (Treg) 的发育. 失去GPR109A会增加Treg细胞,增强对自身免疫性疾病的保护.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 调节性T细胞 (Tregs) 对免疫平衡和预防自身免疫至关重要.
- 外围Treg分化受肠道微生物群代谢物影响,这些代谢物通过像GPR109A.这样的G-蛋白结合受体 (GPCR) 作用.
- 之前,GPR109A在胸腺中部Treg发育中的作用是未知的.
研究的目的:
- 研究GPR109A在胸膜Treg发育中的新型作用.
- 为了确定GPR109A在甲状腺中的细胞表达和功能.
- 评估GPR109A缺乏对自身免疫性疾病模型的影响.
主要方法:
- 在小鼠和人类中单细胞RNA测序以确定GPR109A的表达.
- 在小鼠体内进行流细胞计,以确认GPR109A在胸腺细胞上的表达.
- 在Gpr109a淘汰赛 (Gpr109a-/-) 和野生型 (WT) 小鼠中分析Treg细胞群和自身免疫调节器 (AIRE) 表达.
- 在Gpr109a-/-小鼠中对实验性自身免疫脑膜炎 (EAE) 的评估.
主要成果:
- 在基底条件下,与WT小鼠相比,Gpr109a-/-小鼠在多个器官中表现出增加的Treg细胞.
- GPR109A是表达在骨髓胸膜上皮细胞 (mTECs),而不是T细胞.
- 来自Gpr109a-/-小鼠的mTEC显示出更高的AIRE表达;缺乏GPR109A的WT mTEC也增加了AIRE和增强功能.
- 在Gpr109a-/-小鼠中,胸膜Treg的增加提供了对EAE的保护,减少了临床症状和炎症.
结论:
- 通过调节mTEC功能和AIRE表达,GPR109A在胸膜Treg发育中发挥了新的抑制作用.
- 肠道微生物群可能会通过mTECs上的GPR109A信号来影响胸膜Treg的发育.
- 准GPR109A可能是对自身免疫性疾病的治疗策略.
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