Innate lymphoid cells (ILCs) have emerged as critical regulators of immune defense, tissue repair, and metabolic homeostasis. By integrating environmental cues, they orchestrate tissue-specific metabolic adaptation. This review discusses ILC functions in adult energy regulation and proposes that neonatal ILCs play essential roles in postnatal metabolic and tissue maturation.

ABSTRACT

In the almost two decades since their discovery, innate lymphoid cells (ILCs) have received considerable attention for their roles in immune defense and tissue repair. However, a growing body of evidence now highlights a broader functional spectrum, positioning ILCs as key integrators of environmental cues that support tissue-specific metabolic adaptation. These insights challenge traditional immune-centric paradigms, suggesting that ILCs also contribute to core physiological functions of tissues. In this review, we discuss emerging roles for ILCs in the regulation of energy homeostasis during adulthood, including nutrient sensing, uptake, storage, and utilization. We further examine how these functions may be shaped during the neonatal period, a critical window of developmental transitions that coincides with the establishment of ILC tissue residency. We suggest that ILCs may act as early regulators of postnatal metabolic adaptation, playing a fundamental role in the physiological maturation of tissues after birth.