Autor: |
John Tchen, Quentin Simon, Léa Chapart, Yasmine Lamri, Fanny Saidoune, Emeline Pacreau, Christophe Pellefigues, Julie Bex-Coudrat, Hajime Karasuyama, Kensuke Miyake, Juan Hidalgo, Padraic G. Fallon, Thomas Papo, Ulrich Blank, Marc Benhamou, Guillaume Hanouna, Karim Sacre, Eric Daugas, Nicolas Charles |
Rok vydání: |
2023 |
Popis: |
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering the basophil/TFH cell axis in the SLE context may represent a promising innovative intervention strategy in SLE. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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