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Role of Bcl‐3 in the Development of Follicular Helper T Cells and in the Pathogenesis of Rheumatoid Arthritis

We have previously shown that expression of the Bcl-3 gene, a member of the IκB family, is down-regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl-3 in the pathogenesis of RA. DNA microarray... Full description

Journal Title: Arthritis & Rheumatology October 2015, Vol.67(10), pp.2651-2660
Main Author: Meguro, Kazuyuki
Other Authors: Suzuki, Kotaro , Hosokawa, Junichi , Sanayama, Yoshie , Tanaka, Shigeru , Furuta, Shunsuke , Ikeda, Kei , Takatori, Hiroaki , Suto, Akira , Sakamoto, Akemi , Ohara, Osamu , Nakajima, Hiroshi
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ID: ISSN: 2326-5191 ; E-ISSN: 2326-5205 ; DOI: 10.1002/art.39266
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recordid: wj10.1002/art.39266
title: Role of Bcl‐3 in the Development of Follicular Helper T Cells and in the Pathogenesis of Rheumatoid Arthritis
format: Article
creator:
  • Meguro, Kazuyuki
  • Suzuki, Kotaro
  • Hosokawa, Junichi
  • Sanayama, Yoshie
  • Tanaka, Shigeru
  • Furuta, Shunsuke
  • Ikeda, Kei
  • Takatori, Hiroaki
  • Suto, Akira
  • Sakamoto, Akemi
  • Ohara, Osamu
  • Nakajima, Hiroshi
subjects:
  • Arthritis, Rheumatoid -- Physiopathology
  • Proto-Oncogene Proteins -- Physiology
  • T-Lymphocytes, Helper-Inducer -- Pathology
  • Transcription Factors -- Physiology
ispartof: Arthritis & Rheumatology, October 2015, Vol.67(10), pp.2651-2660
description: We have previously shown that expression of the Bcl-3 gene, a member of the IκB family, is down-regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl-3 in the pathogenesis of RA. DNA microarray analysis was used to compare the signal intensity of Bcl-3 in CD4+ T cells from untreated RA patients and healthy controls. We examined the roles of interleukin-6 (IL-6)/STAT-3 signaling in the induction of Bcl-3. In addition, we analyzed the gene expression profiles of Bcl-3-transduced CD4+ T cells by RNA sequencing. The effects of enforced expression as well as gene silencing of Bcl-3 on the development of follicular helper T (Tfh) cells were evaluated. Finally, we examined correlations between the signal intensities of Bcl-3 and Tfh cell-related genes in CD4+ T cells from untreated RA patients. Bcl-3 levels were significantly higher in RA patients than in healthy controls. IL-6 induced Bcl-3 expression in CD4+ T cells in a STAT-3-dependent manner. Transcriptome analysis revealed that the expression of Bcl-6, a master regulator of Tfh cell differentiation, was significantly up-regulated by the enforced Bcl-3 expression. The enforced Bcl-3 expression increased, but Bcl-3 silencing decreased, the numbers of IL-21-producing Tfh-like cells. Bcl-3 levels in CD4+ T cells from RA patients correlated positively with the levels of Tfh cell-related genes CXCR5, inducible costimulator, and achaete-scute homolog 2. Bcl-3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL-21 production.
language:
source:
identifier: ISSN: 2326-5191 ; E-ISSN: 2326-5205 ; DOI: 10.1002/art.39266
fulltext: fulltext
issn:
  • 2326-5191
  • 23265191
  • 2326-5205
  • 23265205
url: Link


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titleRole of Bcl‐3 in the Development of Follicular Helper T Cells and in the Pathogenesis of Rheumatoid Arthritis
creatorMeguro, Kazuyuki ; Suzuki, Kotaro ; Hosokawa, Junichi ; Sanayama, Yoshie ; Tanaka, Shigeru ; Furuta, Shunsuke ; Ikeda, Kei ; Takatori, Hiroaki ; Suto, Akira ; Sakamoto, Akemi ; Ohara, Osamu ; Nakajima, Hiroshi
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descriptionWe have previously shown that expression of the Bcl-3 gene, a member of the IκB family, is down-regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl-3 in the pathogenesis of RA. DNA microarray analysis was used to compare the signal intensity of Bcl-3 in CD4+ T cells from untreated RA patients and healthy controls. We examined the roles of interleukin-6 (IL-6)/STAT-3 signaling in the induction of Bcl-3. In addition, we analyzed the gene expression profiles of Bcl-3-transduced CD4+ T cells by RNA sequencing. The effects of enforced expression as well as gene silencing of Bcl-3 on the development of follicular helper T (Tfh) cells were evaluated. Finally, we examined correlations between the signal intensities of Bcl-3 and Tfh cell-related genes in CD4+ T cells from untreated RA patients. Bcl-3 levels were significantly higher in RA patients than in healthy controls. IL-6 induced Bcl-3 expression in CD4+ T cells in a STAT-3-dependent manner. Transcriptome analysis revealed that the expression of Bcl-6, a master regulator of Tfh cell differentiation, was significantly up-regulated by the enforced Bcl-3 expression. The enforced Bcl-3 expression increased, but Bcl-3 silencing decreased, the numbers of IL-21-producing Tfh-like cells. Bcl-3 levels in CD4+ T cells from RA patients correlated positively with the levels of Tfh cell-related genes CXCR5, inducible costimulator, and achaete-scute homolog 2. Bcl-3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL-21 production.
subjectArthritis, Rheumatoid -- Physiopathology ; Proto-Oncogene Proteins -- Physiology ; T-Lymphocytes, Helper-Inducer -- Pathology ; Transcription Factors -- Physiology;
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