Chemokines determine local lymphoneogenesis and a reduction of circulating CXCR4+ T and CCR7 B and T lymphocytes in thyroid autoimmune diseases
Chemokines determine local lymphoneogenesis and a reduction of circulating CXCR4+ T and CCR7 B and T lymphocytes in thyroid autoimmune diseases
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DOI：
10.4049/jimmunol.170.12.6320
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发表时间：
2003-06-15
影响因子：
4.4
通讯作者：
Juan, M
中科院分区：
文献类型：
--
作者：
Armengol, MP;Cardoso-Schmidt, CB;Juan, M
趋化因子及其相应的受体对于淋巴细胞向淋巴器官的募集及其在多步骤过程中的组织化至关重要。受自身免疫性疾病影响的组织通常含有异位淋巴滤泡，在自身免疫性甲状腺疾病的情况下，异位淋巴滤泡高度。活性和特异性的甲状腺抗原，但其致病作用尚不清楚。为了了解这些淋巴滤泡的发生，相关细胞因子和趋化因子的表达进行了评估，通过真实的时间PCR，免疫组织化学和体外试验在自身免疫性和非自身免疫性甲状腺。在自身免疫患者的甲状腺中，CXC趋化因子α、CXC趋化因子β、C-C趋化因子配体（CCL）21、CXC趋化因子配体（CXCL）12、CXCL 13和CCL 22水平升高，而在有异位次级淋巴滤泡的自身免疫腺体中，CXCL 12、CXCL 13和CCL 22水平显著高于无滤泡的自身免疫腺体。有趣的是，甲状腺上皮产生CXCL 12响应促炎细胞因子提供了一个可能的线索，了解组织应力如何可能导致异位卵泡形成。趋化因子和甲状腺自身抗体之间的相关性的发现进一步表明，甲状腺内生发中心在自身免疫反应中发挥重要作用。出乎意料的是，与甲状腺内淋巴细胞相比，自身免疫性甲状腺疾病患者PBMC中循环CXCR 4（+）T细胞和CCR 7（+）B和T细胞（但不包括CXCR 5）的百分比显著降低。这种活跃的甲状腺内淋巴组织的全身效应可能成为甲状腺自身免疫性疾病活动的新标志。
Chemokines and their corresponding receptors are crucial for the recruitment of lymphocytes into the lymphoid organs and for its organization acting in a multistep process. Tissues affected by autoimmune disease often contain ectopic lymphoid follicles which, in the case of autoimmune thyroid disorders, are highly. active and specific for thyroid Ags although its pathogenic role remains unclear. To understand the genesis of these lymphoid follicles, the expression of relevant cytokines and chemokines was assessed by real time PCR, immunohistochemistry and by in vitro assays in autoimmune and nonautoimmune thyroid glands. Lymphotoxin alpha, lymphotoxin beta, C-C chemokine ligand (CCL) 21, CXC chemokine ligand (CXCL) 12, CXCL13, and CCL22 were increased in thyroids from autoimmune patients, whereas CXCL12, CXCL13, and CCL22 levels were significantly higher in autoimmune glands with ectopic secondary lymphoid follicles than in those without follicles. Interestingly, thyroid epithelium produced CXCL12 in response to proinflammatory cytokines providing a possible clue for the understanding of how tissue stress may lead to ectopic follicle formation. The finding of a correlation between chemokines and thyroid autoantibodies further suggests that intrathyroidal germinal centers play a significant role in the autoimmune response. Unexpectedly, the percentage of circulating CXCR4(+) T cells and CCR7(+) B and T cells (but not of CXCR5) was significantly reduced in PBMCs of patients with autoimmune thyroid disease when they were compared with their intrathyroidal lymphocytes. This systemic effect of active intrathyroidal lymphoid tissue emerges as a possible new marker of thyroid autoimmune disease activity.