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

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.

SUBMITTER: Bang YJ

PROVIDER: S-EPMC8532503 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Bang Ye-Ji YJ Hu Zehan Z Li Yun Y Gattu Sureka S Ruhn Kelly A KA Raj Prithvi P Herz Joachim J Hooper Lora V LV

Science (New York, N.Y.) 20210917 6561

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 r ...[more]

PMID: 34529485

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