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Interleukin-7 protects against bacterial respiratory infection by promoting IL-17A-producing innate T-cell response

Abstract : Interleukin-7 (IL-7) is a critical cytokine in B- and T-lymphocyte development and maturation. Recent evidence suggests that IL-7 is a preferential homeostatic and survival factor for RORγt+ innate T cells such as natural killer T (NKT) cells, γδT cells, and mucosal-associated invariant T (MAIT) cells in the periphery. Given the important contribution of these populations in antibacterial immunity at barrier sites, we questioned whether IL-7 could be instrumental in boosting the local host immune response against respiratory bacterial infection. By using a cytokine-monoclonal antibody approach, we illustrated a role for topical IL-7 delivery in increasing the pool of RORγt+ IL-17A-producing innate T cells. Prophylactic IL-7 treatment prior to Streptococcus pneumoniae infection led to better bacterial containment, a process associated with increased neutrophilia and that depended on γδT cells and IL-17A. Last, combined delivery of IL-7 and α-galactosylceramide (α-GalCer), a potent agonist for invariant NKT (iNKT) cells, conferred an almost total protection in terms of survival, an effect associated with enhanced IL-17 production by innate T cells and neutrophilia. Collectively, we provide a proof of concept that IL-7 enables fine-tuning of innate T- cell functions. This might pave the way for considering IL-7 as an innovative biotherapeutic against bacterial infection.
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https://www.hal.inserm.fr/inserm-03385211
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Submitted on : Tuesday, October 19, 2021 - 1:56:28 PM
Last modification on : Tuesday, May 17, 2022 - 10:58:36 AM
Long-term archiving on: : Thursday, January 20, 2022 - 7:04:03 PM

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Maya Hassane, youenn Jouan, Florent Creusat, Daphnée Soulard, Chloé Boisseau, et al.. Interleukin-7 protects against bacterial respiratory infection by promoting IL-17A-producing innate T-cell response. Mucosal Immunology, Nature Pub. Group, 2020, 13 (1), pp.128-139. ⟨10.1038/s41385-019-0212-y⟩. ⟨inserm-03385211⟩

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