Science:调控肠道适应性免疫的新机制
  • LRP1在肠道CD11c+ 髓系细胞中高表达,是髓系细胞表面的SAA受体;
  • 髓系细胞中,LRP1能高效结合SAA-视黄醇复合体并介导其内吞,进而诱导视黄醛脱氢酶表达以促进视黄醇转化为视黄酸;
  • 小鼠中,SAA和LRP1介导了维生素A依赖性的肠道适应性免疫(B和T细胞的肠道归巢以及IgA生成),并增强口服免疫后的肠道感染抵抗力;
  • 因此,肠上皮表达的SAA与维生素A代谢物视黄醇形成复合体,被LRP1结合并内吞进肠道髓系细胞,促进生成视黄酸,从而介导维生素A依赖性的肠道适应性免疫。
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mildbreeze
维生素A的代谢物视黄醇对肠道适应性免疫有关键作用,缺乏维生素A可增加肠道感染风险。肠道髓系细胞(如树突状细胞和巨噬细胞)能摄入视黄醇,将其加工成视黄酸(RA),并将生成的RA传递给发育中的B细胞和T细胞,进而促进B细胞和T细胞的肠道归巢、诱导B细胞生成IgA。但目前不清楚的是,视黄醇是如何被转运至髓系细胞中的。血清淀粉样蛋白A(SAA)是肠上皮表达的一种视黄醇结合蛋白,其表达受肠道菌群和膳食维生素A的调控。Science发表的一项最新研究鉴定出SAA的髓系细胞表面受体——低密度脂蛋白受体相关蛋白1(LRP1),并证实其能结合SAA-视黄醇复合体,介导了肠道髓系细胞对视黄醇的摄取。对敲除Saa和髓系细胞特异性敲除Lrp1的小鼠模型的进一步研究,证实了SAA和LRP1在维生素A依赖性的肠道适应性免疫中有关键作用。这些发现扩展了人们对肠道免疫机制的认知,为调节肠道免疫、治疗相关疾病提供了新线索。
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Science [IF:47.728]

Serum amyloid A delivers retinol to intestinal myeloid cells to promote adaptive immunity

血清淀粉样蛋白A向肠髓系细胞提供视黄醇以促进适应性免疫

10.1126/science.abf9232

2021-09-17, Article

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Vitamin A and its derivative retinol are essential for the development of intestinal adaptive immunity. Retinoic acid (RA)–producing myeloid cells are central to this process, but how myeloid cells acquire retinol for conversion to RA is unknown. Here, we show that serum amyloid A (SAA) proteins—retinol-binding proteins induced in intestinal epithelial cells by the microbiota—deliver retinol to myeloid cells. We identify low-density lipoprotein (LDL) receptor–related protein 1 (LRP1) as an SAA receptor that endocytoses SAA-retinol complexes and promotes retinol acquisition by RA-producing intestinal myeloid cells. Consequently, SAA and LRP1 are essential for vitamin A–dependent immunity, including B and T cell homing to the intestine and immunoglobulin A production. Our findings identify a key mechanism by which vitamin A promotes intestinal immunity.

First Authors:
Ye-Ji Bang

Correspondence Authors:
Lora V Hooper

All Authors:
Ye-Ji Bang,Zehan Hu,Yun Li,Sureka Gattu,Kelly A Ruhn,Prithvi Raj,Joachim Herz,Lora V Hooper

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