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Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease
B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5—a gene w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569490/ https://www.ncbi.nlm.nih.gov/pubmed/37841260 http://dx.doi.org/10.3389/fimmu.2023.1276014 |
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author | Ono, Chisato Tanaka, Shinya Myouzen, Keiko Iwasaki, Takeshi Ueda, Mahoko Oda, Yoshinao Yamamoto, Kazuhiko Kochi, Yuta Baba, Yoshihiro |
author_facet | Ono, Chisato Tanaka, Shinya Myouzen, Keiko Iwasaki, Takeshi Ueda, Mahoko Oda, Yoshinao Yamamoto, Kazuhiko Kochi, Yuta Baba, Yoshihiro |
author_sort | Ono, Chisato |
collection | PubMed |
description | B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5—a gene whose homologs are associated with human autoimmune diseases—is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Additionally, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model. Furthermore, an increase in Fcrl5 expression broke B cell anergy and facilitated toll-like receptor signaling. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases. |
format | Online Article Text |
id | pubmed-10569490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105694902023-10-13 Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease Ono, Chisato Tanaka, Shinya Myouzen, Keiko Iwasaki, Takeshi Ueda, Mahoko Oda, Yoshinao Yamamoto, Kazuhiko Kochi, Yuta Baba, Yoshihiro Front Immunol Immunology B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5—a gene whose homologs are associated with human autoimmune diseases—is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Additionally, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model. Furthermore, an increase in Fcrl5 expression broke B cell anergy and facilitated toll-like receptor signaling. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases. Frontiers Media S.A. 2023-09-28 /pmc/articles/PMC10569490/ /pubmed/37841260 http://dx.doi.org/10.3389/fimmu.2023.1276014 Text en Copyright © 2023 Ono, Tanaka, Myouzen, Iwasaki, Ueda, Oda, Yamamoto, Kochi and Baba https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ono, Chisato Tanaka, Shinya Myouzen, Keiko Iwasaki, Takeshi Ueda, Mahoko Oda, Yoshinao Yamamoto, Kazuhiko Kochi, Yuta Baba, Yoshihiro Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease |
title | Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease |
title_full | Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease |
title_fullStr | Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease |
title_full_unstemmed | Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease |
title_short | Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease |
title_sort | upregulated fcrl5 disrupts b cell anergy causes autoimmune disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569490/ https://www.ncbi.nlm.nih.gov/pubmed/37841260 http://dx.doi.org/10.3389/fimmu.2023.1276014 |
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