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BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance
Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. More than 90% of patients with SSc are positive for autoantibodies. In addition, serum B cell activating factor (BAFF) level is correlated with SSc severity and activity. Thus, B cells are considered to play a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040844/ https://www.ncbi.nlm.nih.gov/pubmed/30009261 http://dx.doi.org/10.1126/sciadv.aas9944 |
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author | Matsushita, Takashi Kobayashi, Tadahiro Mizumaki, Kie Kano, Miyu Sawada, Tomoyo Tennichi, Momoko Okamura, Ai Hamaguchi, Yasuhito Iwakura, Yoichiro Hasegawa, Minoru Fujimoto, Manabu Takehara, Kazuhiko |
author_facet | Matsushita, Takashi Kobayashi, Tadahiro Mizumaki, Kie Kano, Miyu Sawada, Tomoyo Tennichi, Momoko Okamura, Ai Hamaguchi, Yasuhito Iwakura, Yoichiro Hasegawa, Minoru Fujimoto, Manabu Takehara, Kazuhiko |
author_sort | Matsushita, Takashi |
collection | PubMed |
description | Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. More than 90% of patients with SSc are positive for autoantibodies. In addition, serum B cell activating factor (BAFF) level is correlated with SSc severity and activity. Thus, B cells are considered to play a pathogenic role in SSc. However, there are two opposing subsets: regulatory B cells (Bregs) and effector B cells (Beffs). Interleukin-10 (IL-10)–producing Bregs negatively regulate the immune response, while IL-6–producing Beffs positively regulate it. Therefore, a protocol that selectively depletes Beffs would represent a potent therapy for SSc. The aims of this study were to investigate the roles of Bregs and Beffs in SSc and to provide a scientific basis for developing a new treatment strategy targeting B cells. A bleomycin-induced scleroderma model was induced in mice with a B cell–specific deficiency in IL-6 or IL-10. We also examined whether BAFF regulates cytokine-producing B cells and its effects on the scleroderma model. IL-6–producing Beffs increased in number and infiltrated the inflamed skin in the scleroderma model. The skin and lung fibrosis was attenuated in B cell–specific IL-6–deficient mice, whereas B cell–specific IL-10–deficient mice showed more severe fibrosis. In addition, BAFF increased Beffs but suppressed Bregs. Furthermore, BAFF antagonist attenuated skin and lung fibrosis in the scleroderma model with reduction of Beffs but not of Bregs. The current study indicates that Beffs play a pathogenic role in the scleroderma model, while Bregs play a protective role. BAFF inhibition is a potential therapeutic strategy for SSc via alteration of B cell balance. |
format | Online Article Text |
id | pubmed-6040844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60408442018-07-15 BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance Matsushita, Takashi Kobayashi, Tadahiro Mizumaki, Kie Kano, Miyu Sawada, Tomoyo Tennichi, Momoko Okamura, Ai Hamaguchi, Yasuhito Iwakura, Yoichiro Hasegawa, Minoru Fujimoto, Manabu Takehara, Kazuhiko Sci Adv Research Articles Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. More than 90% of patients with SSc are positive for autoantibodies. In addition, serum B cell activating factor (BAFF) level is correlated with SSc severity and activity. Thus, B cells are considered to play a pathogenic role in SSc. However, there are two opposing subsets: regulatory B cells (Bregs) and effector B cells (Beffs). Interleukin-10 (IL-10)–producing Bregs negatively regulate the immune response, while IL-6–producing Beffs positively regulate it. Therefore, a protocol that selectively depletes Beffs would represent a potent therapy for SSc. The aims of this study were to investigate the roles of Bregs and Beffs in SSc and to provide a scientific basis for developing a new treatment strategy targeting B cells. A bleomycin-induced scleroderma model was induced in mice with a B cell–specific deficiency in IL-6 or IL-10. We also examined whether BAFF regulates cytokine-producing B cells and its effects on the scleroderma model. IL-6–producing Beffs increased in number and infiltrated the inflamed skin in the scleroderma model. The skin and lung fibrosis was attenuated in B cell–specific IL-6–deficient mice, whereas B cell–specific IL-10–deficient mice showed more severe fibrosis. In addition, BAFF increased Beffs but suppressed Bregs. Furthermore, BAFF antagonist attenuated skin and lung fibrosis in the scleroderma model with reduction of Beffs but not of Bregs. The current study indicates that Beffs play a pathogenic role in the scleroderma model, while Bregs play a protective role. BAFF inhibition is a potential therapeutic strategy for SSc via alteration of B cell balance. American Association for the Advancement of Science 2018-07-11 /pmc/articles/PMC6040844/ /pubmed/30009261 http://dx.doi.org/10.1126/sciadv.aas9944 Text en Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Matsushita, Takashi Kobayashi, Tadahiro Mizumaki, Kie Kano, Miyu Sawada, Tomoyo Tennichi, Momoko Okamura, Ai Hamaguchi, Yasuhito Iwakura, Yoichiro Hasegawa, Minoru Fujimoto, Manabu Takehara, Kazuhiko BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance |
title | BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance |
title_full | BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance |
title_fullStr | BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance |
title_full_unstemmed | BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance |
title_short | BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance |
title_sort | baff inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector b cell balance |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040844/ https://www.ncbi.nlm.nih.gov/pubmed/30009261 http://dx.doi.org/10.1126/sciadv.aas9944 |
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