TACI haploinsufficiency protects against BAFF‐driven humoral autoimmunity in mice
| العنوان: | TACI haploinsufficiency protects against BAFF‐driven humoral autoimmunity in mice |
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| المؤلفون: | Kelly L. Hudkins, David J. Rawlings, Samuel W. Du, Holly M. Jacobs, Shaun W. Jackson, Charles E. Alpers, Quan Zhen Li, Nicole E. Scharping, Tanvi Arkatkar, Jonathan Woods |
| المصدر: | Eur J Immunol |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Transmembrane Activator and CAML Interactor Protein, Immunology, Lupus nephritis, Autoimmunity, Haploinsufficiency, Biology, Antibodies, Monoclonal, Humanized, medicine.disease_cause, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, B-Cell Activating Factor, medicine, Animals, Immunology and Allergy, B-cell activating factor, Mice, Knockout, B-Lymphocytes, Chimera, Common variable immunodeficiency, Autoantibody, Germinal center, medicine.disease, Lupus Nephritis, Mice, Inbred C57BL, 030104 developmental biology, Female, Immunosuppressive Agents, B-Cell Activation Factor Receptor, Signal Transduction, 030215 immunology |
| الوصف: | Polymorphisms in TACI, a BAFF family cytokine receptor, are linked to diverse human immune disorders, including common variable immunodeficiency (CVID) and systemic lupus erythematosus (SLE). Functional studies of individual variants show modest impacts on surface TACI expression and/or downstream signal transduction, indicating that relatively subtle variation in TACI activity can impact human B cell biology. However, significant complexity underlies TACI biology, including both positive and negative regulation of physiologic and pathogenic B cell responses. To model these contradictory events, we compared the functional impact of TACI deletion on separate models of murine SLE driven by T cell-independent and -dependent breaks in B cell tolerance. First, we studied whether reduced surface TACI expression was sufficient to protect against progressive BAFF-mediated systemic autoimmunity. Strikingly, despite a relatively modest impact on surface TACI levels, TACI haploinsufficiency markedly reduced pathogenic RNA-associated autoantibody titers and conferred long-term protection from BAFF-driven lupus nephritis. In contrast, B cell-intrinsic TACI deletion exerted a limited impact of autoantibody generation in murine lupus characterized by spontaneous germinal center formation and T cell-dependent humoral autoimmunity. Together, these combined data provide new insights into TACI biology and highlight how TACI signals must be tightly regulated during protective and pathogenic B cell responses. |
| تدمد: | 1521-4141 0014-2980 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1dbf37ec4020047e8f86ddcf403722a5 https://doi.org/10.1002/eji.202149244 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1dbf37ec4020047e8f86ddcf403722a5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15214141 00142980 |
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