Role of Vitamins in the Control of Immunity

维生素在控制免疫中的作用

• 批准号: 8336342
• 负责人: Yasmine Belkaid
• 金额: $ 53.78万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336342
• 关键词: CD4 Positive T Lymphocytes; Cell physiology; Cells; Defect; Gastrointestinal Diseases; Goals; Gut associated lymphoid tissue; Health; Helper-Inducer T-Lymphocyte; Homeostasis; Human; Immunity; Infection; Mediating; Nutrient; Nutritional status; Oral; Regulatory T-Lymphocyte; Role; Signal Transduction; T cell response; T-Cell Activation; T-Lymphocyte; Therapeutic; Tretinoin; Vaccination; Vaccines; Vitamin A; Vitamins; Work; cell type; in vivo; novel; oral infection; response; retinoic acid receptor alpha

Vitamin A is an essential nutrient that is critical for human health. Recent findings indicate that metabolites of vitamin A, namely retinoic acid, exert immunoregulatory effects through the induction of regulatory T cells and, independently, though suppression of effector T cell responses. However, the paramount role of this vitamin in sustaining protective immunity in humans has not been integrated into these findings. We found that vitamin A insufficiency abrogates CD4+ helper T cell type 1 (TH-1) and type 17 (TH-17) immunity to active infection and oral vaccination. Short-term administration of the vitamin A metabolite, retinoic acid (RA), fully restored TH-1 and TH-17 responses in vivo, and this effect was mediated through retinoic acid receptor alpha (RAR-a). Moreover, deficiency in RAR-a; resulted in a cell autonomous CD4+ T cell activation defect. Altogether, our work reveal a novel and essential role for RA in the promotion of vitamin A dependent immunity via direct effects on effector CD4+ T cell function. They also establish nutritional status as a tuning mechanism for effector T cell responses.

维生素A是对人类健康至关重要的必需营养素。最近的发现表明，维生素A的代谢产物，即视黄酸，通过诱导调节性T细胞以及独立地抑制效应T细胞反应，发挥免疫调节作用。但是，这种维生素在维持人类保护性免疫中的最高作用尚未纳入这些发现。我们发现，维生素A不仅可以消除CD4+辅助T细胞类型1（TH-1）和17型（TH-17）免疫对主动感染和口服疫苗接种的免疫。维生素A代谢物，视黄酸（RA）的短期施用，在体内完全恢复了Th-1和Th-17反应，这种作用是通过视黄酸受体α（RAR-A）介导的。而且，RAR-A缺乏；导致细胞自主的CD4+ T细胞激活缺陷。总的来说，我们的工作揭示了RA通过直接影响效应子CD4+ T细胞功能的直接影响促进维生素A依赖性免疫的新颖而重要的作用。他们还建立了营养状况作为效应T细胞反应的调整机制。