25-hydroxycholesterol: Gatekeeper of intestinal IgA
| Autor: | Christopher Piper, Claudia Mauri |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
B-Lymphocytes
Cholesterol Metabolite Immunology Disease Biology Germinal Center Immune Dysfunction Hydroxycholesterols Article Immunoglobulin A Peyer's Patches chemistry.chemical_compound Infectious Diseases chemistry Immunity Plasma cell differentiation Immunology and Allergy lipids (amino acids peptides and proteins) Transcription factor |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| Popis: | Diets high in cholesterol alter intestinal immunity. Here, we examined how the cholesterol metabolite 25-hydroxycholesterol (25-HC) impacts the intestinal B cell response. Mice lacking cholesterol 25-hydroxylase (CH25H), the enzyme generating 25-HC, had higher frequencies of IgA-secreting antigen-specific B cells upon immunization or infection. 25-HC did not affect class switch recombination, but rather restrained plasma cell (PC) differentiation. 25-HC was produced by follicular dendritic cells and increased in response to dietary cholesterol. Mechanistically, 25-HC restricted activation of the sterol sensing transcription factor SREBP2, thereby regulating B cell cholesterol biosynthesis. Ectopic expression of SREBP2 in germinal center B cells induced rapid PC differentiation, whereas SREBP2 deficiency reduced PC output in vitro and in vivo. High cholesterol diet impaired, whereas Ch25h deficiency enhanced, the IgA response against Salmonella and the resulting protection from systemic bacterial dissemination. Thus, a 25-HC-SREBP2 axis shapes the humoral response at the intestinal barrier, providing insight into the impact of high dietary cholesterol in intestinal immunity. |
| Databáze: | OpenAIRE |
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