title: 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.
abstract: 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.
authors.affiliation: Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China; Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan. Electronic address: menghongxue15@163.com.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China; Department of Pathology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
authors.forename: Huining
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Ohe
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Ye Aung
authors.initials: YA
authors.lastname: Naing
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Suran
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kabasawa
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Osakabe
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Ohtake
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kakehata
authors.affiliation: Department of Pathology, Sendai Shakaihoken Hospital, Sendai, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Joh
authors.affiliation: Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan. Electronic address: k-moh@med.id.yamagata-u.ac.jp.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamakawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000097:blood*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D014066:Palatine Tonsil / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007070:Immunoglobulin A; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; D000094632:Thymic Stromal Lymphopoietin