| RRC ID |
57612
|
| 著者 |
Otsuka K, Yamada A, Saito M, Ushio A, Sato M, Kisoda S, Shao W, Tsunematsu T, Kudo Y, Arakaki R, Ishimaru N.
|
| タイトル |
Achaete-Scute Homologue 2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Murine Model for Sjögren Syndrome.
|
| ジャーナル |
Am J Pathol
|
| Abstract |
Follicular helper T (Tfh) cells contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Herein, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren syndrome (SS) wherein the mice underwent neonatal thymectomy. Germinal center (GC) development was promoted in this SS model along with an increase of Tfh cells and GC B cells. The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. In addition, treatment with an anti-CD20 monoclonal antibody effectively suppressed the autoimmune lesions with a reduction of Tfh cells and GC B cells. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were up-regulated in peripheral CD25- CD4+ T cells in SS model mice compared with those in control mice. Moreover, an experiment using CD4CreBcl6fl/fl mice that received neonatal thymectomy treatment demonstrated that Ascl2 contributes to the Tfh cell differentiation associated with autoimmunity during the early stages, independent of Bcl6. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity.
|
| 巻・号 |
189(12)
|
| ページ |
2414-2427
|
| 公開日 |
2019-12-1
|
| DOI |
10.1016/j.ajpath.2019.08.008
|
| PII |
S0002-9440(19)30712-6
|
| PMID |
31539517
|
| MeSH |
Animals
Autoantibodies / immunology
Autoantibodies / metabolism
Autoimmunity / immunology*
B-Lymphocytes / immunology*
B-Lymphocytes / metabolism
B-Lymphocytes / pathology
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Cell Differentiation
Cytokines / immunology
Cytokines / metabolism
Disease Models, Animal*
Female
Germinal Center / immunology*
Germinal Center / metabolism
Germinal Center / pathology
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-bcl-6 / genetics
Proto-Oncogene Proteins c-bcl-6 / metabolism
Sjogren's Syndrome / immunology*
Sjogren's Syndrome / metabolism
Sjogren's Syndrome / pathology
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Helper-Inducer / metabolism
T-Lymphocytes, Helper-Inducer / pathology
|
| IF |
3.762
|
| 引用数 |
1
|
| リソース情報 |
| 実験動物マウス |
RBRC05663 |
