Publication: Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells

Publié dans: Journal of Experimental Medicine, 2017, 214 (12), pp.3531-3541. ⟨10.1084/jem.20171048⟩

Auteurs: Linda Quatrini, Elisabeth Wieduwild, Sophie Guia, Claire Bernat, Nicolas Glaichenhaus, Eric Vivier, Sophie Ugolini

Résumé

Upon infection, the immune system produces inflammatory mediators important for pathogen clearance. However, inflammation can also have deleterious effect on the host and is tightly regulated. Immune system-derived cytokines stimulate the hypothalamic-pituitary-adrenal (HPA) axis, triggering endogenous glucocorticoid production. Through interaction with ubiquitously expressed glucocorticoid receptors (GRs), this steroid hormone has pleiotropic effects on many cell types. Using a genetic mouse model in which the gene encoding the GR is selectively deleted in NKp46(+) innate lymphoid cells (ILCs), we demonstrated a major role for the HPA pathway in host resistance to endotoxin-induced septic shock. GR expression in group 1 ILCs is required to limit their IFN-gamma production, thereby allowing the development of IL-10-dependent tolerance to endotoxin. These findings suggest that neuroendocrine axes are crucial for tolerization of the innate immune system to microbial endotoxin exposure through direct corticosterone-mediated effects on NKp46-expressing innate cells, revealing a novel strategy of host protection from immunopathology.

Lien vers Pubmed [PMID] – 29141867

Lien vers HAL – amu-01765914

Lien vers le DOI – 10.1084/jem.20171048