Type 2 neuroimmune interaction-mediated functional homeostasis and tissue repair

Abstract The functional interdependence between type 2 immunity and the nervous system plays a critical role in maintaining tissue homeostasis and promoting repair across multiple organs. These systems act in concert through bidirectional crosstalk to preserve systemic physiological equilibrium. The nervous system, including its peripheral components, releases neuropeptides and neurotransmitters in response to signals from type 2 immune cells, such as T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s), thereby inducing cytokine production and immunomodulatory effects. Conversely, type 2 immune cells and their cytokines can sensitize peripheral nociceptors and regulate neurotransmitter release, forming a reciprocal feedback loop. This review summarizes the molecular mechanisms underlying type 2 neuroimmune interactions and their roles in physiological homeostasis and tissue repair across multiple organ systems, including the nervous system, skin, gastrointestinal tract, respiratory tract, and oral cavity. In addition, we highlight current controversies and knowledge gaps to identify critical molecular targets that confer specificity to type 2 neuroimmune interactions, and to propose emerging conceptual frameworks and research directions for the clinical management of related disorders.