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PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus.
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- Author(s): TCHEN, John; SIMON, Quentin; CHAPART, Léa; THAMINY, Morgane K.; VIBHUSHAN, Shamila; SAVEANU, Loredana; LAMRI, Yasmine; SAIDOUNE, Fanny; PACREAU, Emeline; PELLEFIGUES, Christophe; BEX-COUDRAT, Julie; KARASUYAMA, Hajime; MIYAKE, Kensuke; HIDALGO, Juan; FALLON, Padraic G.; PAPO, Thomas; BLANK, Ulrich; BENHAMOU, Marc; HANOUNA, Guillaume; SACRE, Karim
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Nature Communications; 4/22/2024, Vol. 15 Issue 1, p1-18, 18p- Subject Terms:
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- Additional Information
- Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis. Basophils have been implicated in systemic lupus erythematosus (SLE), as evidenced by the fact that basophil-deficient mice do not develop the disease. Here, the authors demonstrate that PD-L1 and IL-4 expression in basophils promotes the pathogenic accumulation of follicular helper T cells in patients with SLE and murine models. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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