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.

Neutrophils, as the rapid response cells of the innate immune system, play a critical role in defending against acute infections and are intricately involved in the bidirectional regulation of neurodegenerative and chronic inflammatory disorders. Emerging evidence indicates neutrophils in the pathogenesis of Alzheimer’s disease (AD) and periodontitis through releasing inflammatory mediators, formation of neutrophil extracellular traps (NETs), and modulation of the local microenvironment. These cells could act as a crucial connection bridging the pathological processes in the brain and the oral cavity. This review explores the presence and functional roles of neutrophils in AD, provides a comprehensive overview of their mechanisms in periodontitis, and summarizes associated clinical detection indicators. Furthermore, it outlines potential neutrophil-mediated pathways that connect periodontitis and AD. By integrating findings from single-cell sequencing, animal models, and clinical data, this review offers new perspectives for early diagnosis and therapeutic intervention in periodontitis to potentially delay the progression of AD. It also highlights the dynamic role of neutrophils as a mechanistic bridge between the two diseases and discusses targeted diagnostic and treatment strategies focused on neutrophil modulation.