Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates with elevated serum immunoglobulin A titer by promoting tonsillar immunoglobulin A class switching in immunoglobulin A nephropathy
Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates with elevated serum immunoglobulin A titer by promoting tonsillar immunoglobulin A class switching in immunoglobulin A nephropathy
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DOI：
10.1016/j.trsl.2016.04.008
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发表时间：
2016-10-01
影响因子：
7.8
通讯作者：
Yamakawa, Mitsunori
中科院分区：
文献类型：
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作者：
Meng, Hongxue;Li, Huining;Yamakawa, Mitsunori
免疫球蛋白A(IgA)肾病(IgAN)以血清IgA水平升高和肾小球系膜沉积为特征。以前的研究表明，血清IgA升高的部分原因是扁桃体。在这里，我们研究了IgA在IgAN患者扁桃体中产生的机制。免疫组织化学结果显示，IgA肾病患者扁桃体中的IgA阳性细胞数量和相对百分率明显增加。与非IgAN患者相比，IgAN患者扁桃体生发中心滤泡树突状细胞(FDCs)中胸腺间质淋巴生成素(TSLP)、TSLP受体(TSLPR)、活化诱导胞苷脱氨酶(AID)、转化生长因子-β1(TGF-β1)、肿瘤坏死因子家族B细胞激活因子(BAFF)和增殖诱导配体(APRIL)表达增强。重要的是，在孤立的FDC相关簇中，TSLP与IgA产生相关。IgAN患者血清TSLP水平升高，并与扁桃体和血清中IgA的过度表达相关。这些数据表明，扁桃体FDCs中TSLP的过度表达可能通过AID、转化生长因子-β1、BAFF和APRIL的协同作用促进IgA肾病患者的IgA类转换。因此，FDCs中TSLP与扁桃体中IgA的相互作用可能是IgAN发病的重要机制之一。
Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. Immunohistochemistry revealed that the number and relative percentage of IgA-bearing cells were significantly increased in the tonsils of IgAN patients. Compared with non-IgAN patients, enhanced IgA class switching and overexpression of thymic stromal lymphopoietin (TSLP), TSLP receptor (TSLPR), activation-induced cytidine deaminase (AID), transforming growth factor-beta 1 (TGF-beta 1), B cell-activating factor of the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL) were detected in follicular dendritic cells (FDCs) of tonsillar germinal centers from IgAN patients. Importantly, TSLP correlated with IgA production in isolated FDC-associated clusters. Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-beta 1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN.