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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• 作者：Hongxue Meng^a ; ^b ; ¹ ; ^{menghongxue15@163.com" class="auth_mail" title="E-mail the corresponding author} ; Huining Li^c ; ^d ; ¹ ; Rintaro Ohe^b ; Ye Aung Naing^b ; Suran Yang^b ; Takanobu Kabasawa^b ; Tomoya Kato^b ; Mitsumasa Osakabe^b ; Hiroya Ohtake^b ; Akihiro Ishida^e ; Junli Lu^a ; Lei Zhang^b ; Nobuo Ohta^e ; Seiji Kakehata^e ; Kensuke Joh^f ; Qingtao Shi^a ; Xiaoming Jin^b ; Jingshu Geng^a ; Mitsunori Yamakawa^b ; ^{k-moh@med.id.yamagata-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AID ; activation-induced cytidine deaminase ; APRIL ; a proliferation-inducing ligand ; BAFF ; B cell-activating factor of the TNF family ; BSA ; bovine serum albumin ; cDNA ; complementary DNA ; CSR ; class switch recombination ; DCs ; dendritic cells ; FBS ; fetal bovine serum ; FDCs ; follicular dendritic cells ; GC ; germinal center ; GLTs ; germline transcripts ; IgAN ; IgA nephropathy ; IHC ; immunohistochemistry ; IL-7Rα ; IL-7 receptor α chain ; ISH ; in situ hybridization ; LCM ; laser capture microdissection ; PBS ; p
• 刊名：Translational Research
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：176
• 期：Complete
• 页码：1-17
• 全文大小：6389 K

文摘

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-β1 (TGF-β1), 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-β1, 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.