PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus

John Tchen, Quentin Simon, Léa Chapart, Morgane K. Thaminy, Shamila Vibhushan, Loredana Saveanu, 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 and Nicolas Charles ()
Additional contact information
John Tchen: Faculté de Médecine site Bichat
Quentin Simon: Faculté de Médecine site Bichat
Léa Chapart: Faculté de Médecine site Bichat
Morgane K. Thaminy: Faculté de Médecine site Bichat
Shamila Vibhushan: Faculté de Médecine site Bichat
Loredana Saveanu: Faculté de Médecine site Bichat
Yasmine Lamri: Faculté de Médecine site Bichat
Fanny Saidoune: Faculté de Médecine site Bichat
Emeline Pacreau: Faculté de Médecine site Bichat
Christophe Pellefigues: Faculté de Médecine site Bichat
Julie Bex-Coudrat: Faculté de Médecine site Bichat
Hajime Karasuyama: Tokyo Medical and Dental University (TMDU)
Kensuke Miyake: Tokyo Medical and Dental University (TMDU)
Juan Hidalgo: Bellaterra Campus
Padraic G. Fallon: Trinity College Dublin
Thomas Papo: Faculté de Médecine site Bichat
Ulrich Blank: Faculté de Médecine site Bichat
Marc Benhamou: Faculté de Médecine site Bichat
Guillaume Hanouna: Faculté de Médecine site Bichat
Karim Sacre: Faculté de Médecine site Bichat
Eric Daugas: Faculté de Médecine site Bichat
Nicolas Charles: Faculté de Médecine site Bichat

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47691-w

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DOI: 10.1038/s41467-024-47691-w

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