Antibody Fc-receptor common gamma chain FcεR1γ stabilizes cell surface receptors in group 3 innate lymphoid cells and promotes anti-infection immunity

Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining mucosal homeostasis and regulating inflammatory diseases, but the molecular mechanisms governing their phenotype and function are not fully understood. Here, we showed that ILC3s highly expressed Fcer1g gene, which encodes the antibody Fc-receptor common gamma chain (FcεR1γ). Genetic perturbation of FcεR1γ led to the absence of critical cell membrane receptors NKp46 and CD16 in ILC3s. Alanine scanning mutagenesis identified two residues in FcεR1γ that stabilize its binding partners. FcεR1γ expression in ILC3s was essential for effective protective immunity against bacterial and fungal infections. Mechanistically, FcεR1γ influenced the transcriptional state and proinflammatory cytokine production of ILC3s, relying on the CD16-FcεR1γ signaling pathway. Overall, our findings highlight the significance of FcεR1γ as an adaptor protein that stabilizes cell membrane partners in ILC3s and promotes anti-infection immunity.