Neuroimmune pathways and allergic disease

There is increasing evidence that the nervous system and immune system are closely interlinked and that their interactions can influence the development of allergic diseases. Immune cells, such as mast cells, dendritic cells (DCs), macrophages, and innate lymphoid cells (ILCs), exhibit bidirectional communication with neurons through cytokines, inflammatory mediators, neuropeptides, and neurotransmitters, 1 Kabata H Artis D Neuro-immune crosstalk and allergic inflammation. J Clin Invest. 2019; 129: 1475-1482 Crossref PubMed Scopus (92) Google Scholar linking immune dysregulation with subsequent allergic symptoms such as gastrointestinal (GI) pain, cough, wheezing, and pruritus (Fig 1). Neuropeptides such as substance P (SP) are released in response to inflammation and can activate multiple immune cell types, including T cells, macrophages, DCs, and mast cells. Conversely, immune cells, such as activated mast cells, release inflammatory mediators that stimulate nerve endings, augment neural excitability, and change neuronal gene expression and neuronal signaling, resulting in clinical symptoms such as rhinorrhea, sneezing, coughing, and bronchoconstriction. 2 Kadowaki M Yamamoto T Hayashi S Neuro-immune crosstalk and food allergy: focus on enteric neurons and mucosal mast cells. Allergol Int. 2022; 71: 278-287 Crossref PubMed Scopus (6) Google Scholar The interactions between neurons and immune cells often result in a positive feedback loop in local tissues, amplifying robust immune reactions, which may be responsible for persistent allergic symptoms. Expanding our understanding of neuroimmune crosstalk would be vital in facilitating the development of novel targeted interventions and enhancing the management of allergic diseases and symptoms.