Citrulline enteral administration markedly reduces immunosuppressive extrafollicular plasma cell differentiation in a preclinical model of sepsis - Université de Rennes Accéder directement au contenu
Article Dans Une Revue European Journal of Immunology Année : 2023

Citrulline enteral administration markedly reduces immunosuppressive extrafollicular plasma cell differentiation in a preclinical model of sepsis

Résumé

The sustained immunosuppression associated with severe sepsis favours an increased susceptibility to secondary infections and remains incompletely understood. Plasmablast and plasma cell subsets, whose primary function is to secrete antibodies, have emerged as important suppressive populations expanded during sepsis. In particular, sepsis supports CD39(hi) plasmablast metabolic reprogramming associated with adenosine-mediated suppressive activity. Arginine deficiency has been linked to increased risk of secondary infections in sepsis. Overcoming arginine shortage by citrulline administration efficiently improves sepsis-induced immunosuppression and secondary infections in the cecal ligation and puncture murine model. Here we aimed to determine the impact of citrulline administration on B cell suppressive responses in sepsis. We demonstrate that restoring arginine bioavailability through citrulline administration, markedly reduces the dominant extrafollicular B cell response, decreasing the immunosuppressive LAG3(+) and CD39(+) plasma cell populations, and restoring splenic follicles. At the molecular level, the IRF4/MYC-mediated B cell reprogramming required for extrafollicular plasma cell differentiation is shunted in splenic B cells of mice fed with citrulline. Our study reveals a prominent impact of nutrition on B cell responses, and plasma cell differentiation and further supports the development of citrulline-based clinical studies to prevent sepsis associated immune dysfunction.

Domaines

Cancer Immunologie
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Origine : Publication financée par une institution

Dates et versions

hal-03923239 , version 1 (04-07-2023)

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Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

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Juliette Gauthier, Murielle Grégoire, Florian Reizine, Mathieu Lesouhaitier, Yoni Desvois, et al.. Citrulline enteral administration markedly reduces immunosuppressive extrafollicular plasma cell differentiation in a preclinical model of sepsis. European Journal of Immunology, 2023, 53 (3), pp.2250154. ⟨10.1002/eji.202250154⟩. ⟨hal-03923239⟩
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