Upregulated Fcrl5 disrupts B cell anergy and 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1276014/full |
| _version_ | 1827387543553835008 |
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| author | Chisato Ono Shinya Tanaka Keiko Myouzen Takeshi Iwasaki Mahoko Ueda Yoshinao Oda Kazuhiko Yamamoto Yuta Kochi Yoshihiro Baba |
| author_facet | Chisato Ono Shinya Tanaka Keiko Myouzen Takeshi Iwasaki Mahoko Ueda Yoshinao Oda Kazuhiko Yamamoto Yuta Kochi Yoshihiro Baba |
| author_sort | Chisato Ono |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-08T16:03:45Z |
| format | Article |
| id | doaj.art-a234cc3fadbb43ac865e2196a80d4551 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T16:03:45Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a234cc3fadbb43ac865e2196a80d45512024-01-08T09:44:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12760141276014Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune diseaseChisato Ono0Shinya Tanaka1Keiko Myouzen2Takeshi Iwasaki3Mahoko Ueda4Yoshinao Oda5Kazuhiko Yamamoto6Yuta Kochi7Yoshihiro Baba8Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, JapanDivision of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, JapanLaboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanLaboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanDepartment of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanDivision of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, JapanB 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1276014/fullFc receptor-like 5 (Fcrl5)B cellsage/autoimmunity-associated B cellsautoimmunityimmune toleranceanergy |
| spellingShingle | Chisato Ono Shinya Tanaka Keiko Myouzen Takeshi Iwasaki Mahoko Ueda Yoshinao Oda Kazuhiko Yamamoto Yuta Kochi Yoshihiro Baba Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease Frontiers in Immunology Fc receptor-like 5 (Fcrl5) B cells age/autoimmunity-associated B cells autoimmunity immune tolerance anergy |
| title | Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease |
| title_full | Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease |
| title_fullStr | Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease |
| title_full_unstemmed | Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease |
| title_short | Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease |
| title_sort | upregulated fcrl5 disrupts b cell anergy and causes autoimmune disease |
| topic | Fc receptor-like 5 (Fcrl5) B cells age/autoimmunity-associated B cells autoimmunity immune tolerance anergy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1276014/full |
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