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通过CHOP介导的IL-23过度表达不会导致实验性脊柱关节炎中的结肠炎

Fatemeh Navid¹, Tejpal Gill², Lilah Fones²

¹Pediatric Translational Research Branch, NIAMS, NIH, Bethesda, MD, 20892, USA. fatemeh.navid@nih.gov.

Scientific reports

|May 29, 2024

概括

删除转录因子CHOP并没有减少HLA-B27转基因大鼠的肠道炎症. 相反,CHOP缺乏症加剧了炎症,这表明HLA-B27不会通过ER压力诱导的IL-23引起肠道疾病.

科学领域:

免疫学免疫学免疫学
遗传学是一个遗传学.
胃肠病学胃肠病学

背景情况:

人类白细胞抗原B27 (HLA-B27) 是脊椎关节炎 (SpA) 的重要危险因素.
细胞内膜网膜 (ER) 应激和随后的干白素-23 (IL-23) 生产是驱动SpA病变的假设机制.
转基因HLA-B27 (Tg) 的老鼠表现出SPA特征,包括肠道炎症.

研究的目的:

研究转录因子CHOP (ER压力诱导IL-23的媒介) 在HLA-B27Tg大鼠肠道炎症中的作用.
为了确定删除CHOP是否会影响IL-23的产生和肠道炎症,在这个SPA模型中.

主要方法:

生成的CHOP缺乏的 (Ddit3-/-) HLA-B27 Tg大鼠.
评估了巨细胞和结肠免疫细胞中IL-23的产生.
在结肠中分析基因表达 (转录组) 和组织学分数.
利用RNAScope定位Il17a mRNA和CD3+ T细胞在自己的结肠膜中.

主要成果:

CHOP缺乏消除了ER压力介导的巨细胞中的Il23a过度表达,并减少了结肠免疫细胞中的Il23a表达.
肠道炎症没有减少;相反,在CHOP缺乏HLA-B27Tg的老鼠中,促炎性基因表达 (Il1a,Ifng,Tnf) 和组织损伤得分增加.
Il17a mRNA和CD3+ T细胞的局部化在CHOP的存在和缺席中保持相似.

结论:

在HLA-B27 Tg大鼠中,CHOP缺乏会加剧,而不是改善肠道炎症.
这些发现表明,HLA-B27不会通过主要通过ER压力诱导的IL-23促进肠道疾病.
CHOP可能对更严重的HLA-B27诱导的肠道炎症起着保护作用.

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