血清淀粉样蛋白 A 将视黄醇递送至肠道髓系细胞以促进适应性免疫。
Serum amyloid A delivers retinol to intestinal myeloid cells to promote adaptive immunity.
机构信息
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Science. 2021 Sep 17;373(6561):eabf9232. doi: 10.1126/science.abf9232.
Abstract
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.
摘要
维生素 A 及其衍生物视黄醇对于肠道适应性免疫的发育至关重要。产生视黄酸 (RA) 的髓样细胞是这一过程的核心，但髓样细胞如何获得视黄醇以转化为 RA 尚不清楚。在这里，我们表明血清淀粉样蛋白 A（SAA）蛋白——由肠道上皮细胞在微生物群的刺激下产生的视黄醇结合蛋白——将视黄醇递送给髓样细胞。我们确定 LDL 受体相关蛋白 1 (LRP1) 是 SAA 的受体，它可以内吞 SAA-视黄醇复合物，并促进 RA 产生的肠道髓样细胞获取视黄醇。因此，SAA 和 LRP1 对于依赖维生素 A 的免疫至关重要，包括 B 和 T 细胞归巢到肠道和免疫球蛋白 A 的产生。我们的发现确定了维生素 A 促进肠道免疫的关键机制。
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