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

Linda Quatrini (1) , Elisabeth Wieduwild (1) , Sophie Guia (1) , Claire Bernat (1) , Nicolas Glaichenhaus (2, 3) , Eric Vivier (1) , Sophie Ugolini (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 IPMC - Institut de pharmacologie moléculaire et cellulaire
3 Immunologie des muqueuses et inflammation

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.

Domains: Life Sciences [q-bio]; Immunology; Life Sciences [q-bio]; Human health and pathology; Endocrinology and metabolism

Linda Quatrini, Elisabeth Wieduwild, Sophie Guia, Claire Bernat, Nicolas Glaichenhaus, et al.. Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells. Journal of Experimental Medicine, 2017, 214 (12), pp.3531-3541. ⟨10.1084/jem.20171048⟩. ⟨hal-01764683⟩