T-follicular regulatory cells expand to control germinal center plasma cell output but fail to curb autoreactivity.
| Autor: | Fahlquist-Hagert C; Laboratory for Lymphocyte Biology, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Wittenborn TR; Laboratory for Lymphocyte Biology, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Pedersen MK; Laboratory for Lymphocyte Biology, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Jensen L; Laboratory for Lymphocyte Biology, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Degn SE; Laboratory for Lymphocyte Biology, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2024 Sep 04; Vol. 27 (10), pp. 110887. Date of Electronic Publication: 2024 Sep 04 (Print Publication: 2024). |
| DOI: | 10.1016/j.isci.2024.110887 |
| Abstrakt: | Autoantibodies generated in germinal centers (GCs) contribute to the pathogenesis of autoimmune diseases. GCs are controlled by specialized FoxP3+ T-follicular regulatory cells (Tfr), but their role in established autoimmunity is unclear. We generated autoimmune bone marrow chimeras in which Tfr could be specifically ablated by diphtheria toxin. Furthermore, we tracked the clonal persistence and evolution of Tfr populations using Confetti reporters. Ablation of Tfr caused increased early plasma cell output, but longer-term ablation did not increase plasma cell levels beyond those of Tfr-sufficient controls, suggesting that Tfr fail to contain chronic autoreactive GC responses. In agreement, Tfr were robustly induced in early autoreactive GCs but then waned. Moreover, we observed polyclonal Tfr expansion when ablating part of the Tfr subset. Hence, under homeostatic conditions, a polyclonal population of Tfr operates to control autoreactivity by limiting the output of plasma cells from GCs, but in chronic autoimmunity, this mechanism fails. Competing Interests: The authors declare that they have no conflicts of interest in relation to the presented work. (© 2024 The Author(s).) |
| Databáze: | MEDLINE |
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