Innate immunity is not merely an early defensive system but a key regulator of adaptive immune fate. Through pattern-recognition receptor signaling, antigen presentation, cytokine production, and metabolic–epigenetic reprogramming, innate immune responses shape the strength, duration, and direction of T- and B-cell immunity. This review summarizes how innate immune regulation of adaptive immunity contributes to immune dysregulation in infection, autoimmunity, and allergic disease. We focus on three major mechanisms: remodeling of antigen presentation and costimulation, reshaping of cytokine microenvironments that guide T helper cell polarization, and metabolic–epigenetic programming associated with trained immunity or immune tolerance. We further propose that disease outcomes can be interpreted through three regulatory dimensions of innate immune signaling: insufficient signal strength promotes defective pathogen control and weak adaptive priming; persistent or excessive activation sustains autoimmune inflammation and loss of tolerance; and type 2–biased epithelial–innate signaling drives allergic inflammation through the alarmin–ILC2–Th2–IgE axis. By integrating molecular signaling, innate immune cell crosstalk, metabolic regulation, and epigenetic remodeling, this review provides a concise framework for understanding how innate immune imbalance shapes adaptive immune dysfunction and highlights therapeutic opportunities targeting interferon pathways, inflammasomes, epithelial alarmins, metabolic programs, and microbiome-related immune regulation.
Zhang et al. (2026) studied this question.