Acute stress alleviates type 2 lung inflammation by restricting ILC2s through corticosterone-glucocorticoid receptor signaling

The psychological state profoundly influences immune responses. While chronic stress is generally known to exacerbate inflammation, the impact of acute stress on inflammation has received far less attention. Here, we report that acute stress suppressed group 2 innate lymphoid cell (ILC2) responses, thereby alleviating type 2 lung inflammation. Restraint stress-induced acute stress activated the hypothalamic-pituitary-adrenal (HPA) axis and subsequently increased corticosterone levels. Corticosterone protected mice against lung inflammation by limiting ILC2 proliferation and type 2 cytokine production via the Glucocorticoid Receptor (GR). Adrenalectomy and genetic perturbation of the GR in ILC2s abolished acute stress-mediated immunosuppressive effects. Mechanistic studies revealed that corticosterone-GR signaling impaired ILC2 responses to microenvironmental factors by dampening downstream NF-κB and JAK-STAT signaling. Collectively, these findings reveal that acute stress alleviates ILC2-mediated lung inflammation through the neuroendocrine circuit and demonstrate the inhibitory role of endogenous corticosterone in ILC2 responses.