Lymphoid neogenesis and CD4+T cell differentiation in primary Sjogren's syndrome

原发性干燥综合征中的淋巴新生和 CD4 T 细胞分化

• 批准号: 7687681
• 负责人: Insoo Kang
• 金额: $ 25.49万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687681
• 关键词: Address; Antigen Presentation; Antinuclear Antibodies; Archives; Autoantibodies; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Biopsy; Boxing; CD4 Positive T Lymphocytes; CD4/CD8 ratio procedure; CD8B1 gene; Cell Differentiation process; Cells; Characteristics; Chronic; Defect; Dendritic Cells; Development; Diagnosis; Disease; Effector Cell; Environment; Epitopes; Equilibrium; Figs - dietary; Follicular Dendritic Cells; Frequencies; Fresh Tissue; Gene Expression; Generations; Helper-Inducer T-Lymphocyte; High Endothelial Venule; Homing; IL2RA gene; Immune; Immune Tolerance; Immune response; Immunity; Infiltration; Inflammation; Inflammatory; Injury; Interleukin-1; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-6; Lacrimal gland structure; Lead; Ligands; Light; Link; Location; Lymphatic vessel; Lymphocyte; Lymphoid; Lymphoid Tissue; Measures; Mediating; Memory; Messenger RNA; Methods; Minor; Minor salivary gland structure; Organ; Paper; Pathogenesis; Pathologic; Patients; Phenotype; Population; Process; Production; Recruitment Activity; Regulation; Reporting; Role; Salivary; Salivary Glands; Secondary to; Site; Sjogren' s Syndrome; Spleen; Structure of germinal center of lymph node; Study models; Surrogate Markers; Syndrome; T memory cell; T-Lymphocyte; TALL-1 protein; Th1 Cells; Th2 Cells; Thymus Gland; Tissues; Tumor Necrosis Factor-Beta; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Xerophthalmia; Xerostomia; base; cell type; chemokine; cohort; cytokine; eye dryness; interest; interleukin-23; lymph nodes; memory CD4 T lymphocyte; migration; peripheral blood; receptor

Primary Sjogren's syndrome (pSS) is a systemic chronic inflammatory autoimmune disease characterized by dry eyes and dry mouth. Essential histopathologic features of pSS include focal infiltrations of T and B cells in the salivary and lacrimal glands that lead to tissue injury and chronic inflammation. In some cases, the histopathologic changes develop into tertiary lymphoid tissues or organs (TLs) via a process called lymphoid neogenesis. TLOs resemble spleen and lymph nodes in their cellular composition and organization. TLOs may serve as a place where recruitment of T cells with lymphoid homing capacity (naive and central memory cells) as well as their activation, proliferation and differentiation occur. CD4+ T cells that orchestrate immune responses can be divided into T-helper (Th)1, Th2 and Th17 cells as well as CD4+ T cells with regulatory function including forkhead box P3 (FOXP3)-positive regulatory T cells (Treg). Although T cells and their cytokines are found in the salivary tissues of pSS, it is unknown which type of T cells has a leading role in the pathogenesis. This project investigates the hypothesis that patients with pSS have an altered balance of Th17 and Treg immune responses that is caused by chronic inflammation with lymphoid neogenesis and defect(s) in differentiating and functioning of Th17 cells and Treg based on the facts that Th17 cells potently induce inflammation while Treg suppress it. Plus, the both cell types are linked with autoimmunity and have a reciprocal relationship in cellular differentiation under inflammatory milieu. The hypothesis will be addressed with: 1) Aim 1. Determine if the TLOs in pSS could serve as sites of antigen presentation for induction of autoantibodies, tolerance or activation, focusing on Treg and Th17 cells; 2) Aim 2. Determine if patients with pSS have an altered balance of Th17 and Treg immune responses in the peripheral blood secondary to a defect(s) in Th17 cells and Treg differentiation and function; and 3) Aim 3. Determine if the altered balance of Th17 and Treg immune responses in peripheral blood correlates with TLOs in the fresh minor salivary tissues in patients with pSS. These studies will shed new light on the pathogenesis and treatment of autoimmune diseases including pSS.

原发性干燥综合征（pSS）是一种全身性慢性炎症性自身免疫性疾病