Decreased expression of follicular dendritic cell–secreted protein correlates with increased immunoglobulin A production in the tonsils of individuals with immunoglobulin A nephropathy

Meng, Hongxue; Li, Hui-Ning; Geng, Jiashi; Ohe, Rintaro; Xiaoqiang, E; Ye, Fei; Yang, Suran; Kato, Tomoya; Zhang, Lei; Ishida, Akihiro; Ohta, Nobuo; Jin, Xiaoming; Kakehata, Seiji; Yamakawa, Mitsunori

doi:10.1016/j.trsl.2015.04.004

Cited by 15 publications

(15 citation statements)

References 27 publications

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“…Approximately 50% of the IgAN patients will develop into ESRD [38]. Recent research has indicated that the nephropathic IgA antibodies were probably secreted from palatine tonsils [39]. After α-HS infection, TMCs can undergo ER stress and the following responses could help with the recovery of homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2α Phosphorylation

Peng

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tonsillectomy may be an important method to achieve a long-term remission of IgAN, but patients’ physical status may limit their access to this surgery. We proposed an encouraging solution through inhibiting GADD34 expression in order to promote tonsillar mononuclear cells (TMCs) apoptosis and reduce nephropathic IgA secretion. Methods: A total of 12 IgAN and 9 non-IgAN patients were involved from March 2015 to May 2016. After TMCs were extracted by density gradient centrifugation and stimulated by inactivated hemolytic streptococcus, the mRNA and protein expression of GADD34, GRP78, CHOP, Bcl-2, Bcl-XL, AID, Iα-Cα, and cleaved caspase-3 were examined by fluorescent RT-PCR and Western blotting. Guanabenz treatment and siRNA interference were applied to downregulate GADD34 in tonsillar mononuclear cells from IgAN patients, and P-eIF2α expression was examined by Western Blotting. Cell apoptosis was evaluated by Annexin V FITC/PI flowcytometry, and IgA secretion in cultural supernatant was inspected by enzyme linked immunosorbent assay. Results: After stimulation, the expression of GADD34 was significantly increased in IgAN patients (P< 0.05). Cell apoptosis was mitigated and IgA secretion level was elevated (P< 0.05). To be noticed, CHOP expression had no significant difference between two groups. After guanabenz treatment and siRNA interference, a prolonged elevation of P-eIF2α expression was observed. Cell apoptosis was reinforced and IgA secretion level was decreased (P< 0.05). Conclusion: GADD34 may be a potential therapeutic target for IgAN treatment due to its effect on cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2α Phosphorylation

Peng

Yang

et al. 2018

Cell Physiol Biochem

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“…The few studies performed to understand the functions of this protein suggest that it can modulate B-cell immune response [26–27] and may have a role in autoimmune diseases [28–29]. SRGN is an intracellular proteoglycan implicated in secretory granules formation and immune response modulation as demonstrated in knock-out mouse models [30–31].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing

et al. 2017

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Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas. FDC secreted protein (FDCSP) and Serglycin (SRGN) proved to be specific markers of FDC and related tumor. They showed better specificity and sensitivity values than some well known markers used in FDC sarcoma diagnosis (specificity: 98.6%, and 100%, respectively; sensitivity: 72.73% and 68.18%, respectively). In our cohorts CXCL13, CD21, CD35, FDCSP and SRGN were the best markers for FDC-sarcoma diagnosis and could discriminate 21/22 FDC sarcomas from other mesenchymal tumors by linear discriminant analysis. In summary, by WTS we identified two novel FDC markers and by the analysis of a wide cohort of cases and controls we propose an efficient marker panel for the diagnosis of this rare and enigmatic tumor.

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“…Immunostaining was performed as previously described and used antibodies specific for ERα (EP1; rabbit IgG, DAKO, Agilent Technologies, Santa Clara, California), phosphorylated ERα [pER (ser118)] (16J4; mouse IgG2b, Cell Signaling Technology, Danvers, Massachusetts), PgR (PgR 636; mouse IgG1κ, DAKO, Agilent Technologies), CD21 (1F8; mouse IgG1κ, DAKO, Agilent Technologies), CD23 (DAK‐CD23; mouse IgG1κ, DAKO, Agilent Technologies), CD23 (SP23; rabbit IgG, Nichirei, Tokyo, Japan), CD35 (RLB25; mouse IgG2b, Novocastra, Leica Biosystems, Nussloch, Germany), Clusterin (7D1; mouse IgG1κ, Novocastra, Leica Biosystems), and Podoplanin (D2‐40; mouse IgG1κ, DAKO, Agilent Technologies). Single immunostaining for ERα, PgR, CD21, and CD23 was performed using an Autostainer Link 48 system (Agilent Technologies), while immunostaining for pER was performed manually.…”

Section: Methodsmentioning

confidence: 99%

“…Immunostaining was performed as previously described 12 for ERα, PgR, CD21, and CD23 was performed using an Autostainer Link 48 system (Agilent Technologies), while immunostaining for pER was performed manually. The estimation of the reactivity is described below.…”

Section: Immunostainingmentioning

confidence: 99%

Differential expression of estrogen receptor–α on follicular dendritic cells from patients with grade 1‐2 and grade 3 follicular lymphoma

Ohe

Meng

Aung

et al. 2019

Hematological Oncology

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Hormone therapy has been used for patients with estrogen receptor alpha (ERα)–positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B‐cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1‐3 of FL. Reverse transcription–polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα‐positive cells strongly correlated with the width of GCs ( r s = 0.81, P < 0.01) and the CD21‐positive ( r s = 0.69, P < 0.01) and CD23‐positive ( r s = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα‐positive cells, smaller GCs, and a looser CD21‐ and CD23‐positive FDC meshwork with hormone therapy than without hormone therapy ( P < 0.01). Neoplastic follicles of G1‐2 FL had more ERα‐positive cells and a larger CD23 + FDC meshwork than those of G3 FL ( P < 0.01). ERα mRNA was detected in both G1‐2 FL and G3 FL by reverse transcription–polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα‐positive FDCs and that the responses mediated by the estrogen‐ERα interaction on FDCs may differ between G1‐2 FL and G3 FL.

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Decreased expression of follicular dendritic cell–secreted protein correlates with increased immunoglobulin A production in the tonsils of individuals with immunoglobulin A nephropathy

Cited by 15 publications

References 27 publications

Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2α Phosphorylation

Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2α Phosphorylation

Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing

Differential expression of estrogen receptor–α on follicular dendritic cells from patients with grade 1‐2 and grade 3 follicular lymphoma

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