The neuro-immune regulation is associated with homeostasis of the intestine. Intestinal group 3 innate lymphoid cells (ILC3s) are tissue-resident lymphocytes whose functions are affected by the intestine niche. However, how a gut neuronal signal coordinates the immune response of ILC3s is largely unknown. Here, we found that cyclic adenosine monophosphate (cAMP) signaling exacerbated the inflammatory response and attenuated the expression level of the transcription factor forkhead box O1 (FOXO1) in ILC3s. Deficiency of FOXO1 drove the hyperactivation of ILC3s and resulted in gut inflammation independently of T cells. Mechanistically, FOXO1 promoted the transcription of neuropeptide receptor VIPR2 and inhibited the transcription of adrenoceptor ADRA2A in ILC3s. FOXO1-related regulation of VIPR2 and ADRA2A signaling balanced the activation of ILC3s under steady condition or during colitis. Moreover, chronic stress elevated cAMP level and downregulated FOXO1 level, exacerbating intestinal inflammation. Our findings reveal that FOXO1 balances the activation of ILC3s via VIP and adrenergic signaling and regulates intestinal homeostasis.
Congratulations to Professor Shuo Wang and co-authors from Institute of Microbiology, Chinese Academy of Sciences (Beijing, China) for their wonderful work published in J Exp Med (IF=17.58)!
InvivoChem is proud to provide Professor Shuo Wang’s team with our high-quality product Yohimbine HCl (Cat #: V1127; CAS #: 65-19-0, alpha 2-adrenoreceptor antagonist) for this research.
References: J Exp Med. 2023 Oct 2;220(10):e20230133. doi: 10.1084/jem.20230133.