Exploring the dynamic responses of group 3 innate lymphoid cells at different times in response to LPS challenge

Group 3 innate lymphoid cells (ILC3s) have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. This study aimed to demonstrate the dynamic responses of ILC3s to acute inflammation upon LPS challenge. Microarray data and single-cell RNA sequencing (scRNA-seq) data obtained from the GEO database were combined to analyze the function of ILC3 subset, confirmed by flow cytometry assay and qRT-PCR. The gene enrichment analysis of intersected genes identified between microarray data in bacterial pneumonia and single-cell RNA sequencing of intestinal ILC3s were closely related to TNF-alpha effects on cytokine activity, cell motility and apoptosis pathway, indicating the possibility of intestinal ILC3s migration to the lung. Furthermore, the cellular landscapes of ILC3s in lung and intestine at different times after pulmonary infection exhibited varied ILC3 statuses. ILC3s in lung expanded a lot at 48 h while intestinal ILC3s decreased at 72 h response to LPS challenge, with higher expression of marked genes related to TNF-alpha effects on cytokine activity, cell motility and apoptosis pathway. The main findings in our study may serve as valuable resources for understanding the roles that ILC3s play upon LPS challenge, which may offer opportunities for translating ILC3s as therapeutic targets to regulate LPS-induced pulmonary inflammation.