Dissecting the Roles of Vitamin A in Autoimmunity

剖析维生素 A 在自身免疫中的作用

• 批准号: 9303584
• 负责人: Xin M Luo
• 金额: $ 45.07万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303584
• 关键词: Adjuvant; Affect; Agonist; Alpha Cell; Anti-Inflammatory Agents; Anti-inflammatory; Antigen Presentation; Antigen Targeting; Antigen-Presenting Cells; Attenuated; Autoimmune Diseases; Autoimmune Process; Autoimmune Responses; Autoimmunity; B-Lymphocytes; Biological Process; Cause of Death; Chemicals; Chronic; Complex; Development; Disease; Disease Progression; Disease model; Dose; Environment; Flare; Genes; Immune Tolerance; Immune response; Immune system; Immunologic Adjuvants; Immunosuppressive Agents; Infection; Inflammation; Inflammatory; Inflammatory Response; Laboratories; Ligation; Literature; Lupus; Maintenance; Mediating; Modeling; Molecular; Molecular Mechanisms of Action; Mus; Outcome; Patients; Phase; Play; Process; Reaction Time; Research; Research Project Grants; Role; Severities; Supplementation; Symptoms; Systemic Lupus Erythematosus; T-Lymphocyte; Testing; Time; Transcriptional Regulation; Tretinoin; United States; Vitamin A; base; cell type; design; disability; immunogenic; immunoregulation; knock-down; loss of function; lupus-like; mouse model; neutrophil; novel; prevent; receptor; retinoic acid receptor alpha; undergraduate student

Project Summary Vitamin A and its active metabolite, retinoic acid (RA), are known to exert both pro-inflammatory and anti-inflammatory functions depending on different contexts. RA can suppress inflammation and induce tolerance under steady state. Paradoxically, it can also act as an adjuvant to promote ongoing inflammation against infections. This conundrum on the functions of RA is much less understood for autoimmunity. Evidence is lacking on whether and how RA affects the initiation and progression of autoimmune disorders, which as a whole are a leading cause of death and disability in the United States. In the proposed research, we aim to define the complex roles of RA in autoimmunity. Based on the literature and our preliminary results, we hypothesize that the effects of RA on autoimmune responses are dependent on the stage of disease and that RA suppresses the initiation of autoimmunity but promotes its progression. Using systemic lupus erythematosus (lupus) as our disease model of autoimmunity, we plan to achieve two aims to test this hypothesis. Aim 1 is to determine whether RA suppresses inflammation to prevent the initiation of lupus and delineate a molecular mechanism of action. As our preliminary results have shown that RA exacerbates lupus that is already initiated, Aim 2 is to determine the mechanism by which RA promotes inflammation in the continuation phase of autoimmune lupus. Successful completion of this study will elucidate the complex roles of RA in autoimmunity and provide much needed information concerning the use of, or avoidance of, vitamin A supplementation in lupus patients. Such information may help decrease the occurrence and/or severity of inflammatory flares suffered by these patients.

项目概要 众所周知，维生素 A 及其活性代谢物视黄酸 (RA) 具有促炎和抗炎作用。 抗炎功能根据不同情况而定。 RA可以抑制炎症并 诱导稳态下的耐受性。矛盾的是，它也可以作为促进持续发展的佐剂。 炎症对抗感染。对于 RA 功能的这个难题，人们的理解要少得多。 自身免疫。缺乏证据表明 RA 是否以及如何影响 RA 的发生和进展 自身免疫性疾病，总体而言是美国死亡和残疾的主要原因 国家。在拟议的研究中，我们的目标是明确 RA 在自身免疫中的复杂作用。基于 根据文献和我们的初步结果，我们假设 RA 对自身免疫的影响 反应取决于疾病的阶段，并且 RA 会抑制 自身免疫，但促进其进展。使用系统性红斑狼疮（狼疮）作为我们的 在自身免疫疾病模型中，我们计划实现两个目标来检验这一假设。目标 1 是 确定 RA 是否抑制炎症以预防狼疮的发生并描绘一个 分子作用机制。我们的初步结果表明 RA 会加剧狼疮 目标 2 是确定 RA 促进炎症的机制 自身免疫性狼疮的持续阶段。成功完成这项研究将阐明 RA 在自身免疫中的复杂作用，并提供有关使用的急需信息，或 避免狼疮患者补充维生素A。此类信息可能有助于减少 这些患者所遭受的炎症发作的发生和/或严重程度。