Allergic rhinitis is a common upper airway disease caused by hypersensitivity to various aeroallergens. It causes increased inflammation throughout the body and may be complicated by other otolaryngological pathologies such as chronic hyperplastic eosinophilic sinusitis, nasal polyposis, and serous otitis media. Allergic rhinitis is an IgE-mediated disease and immunotherapy can be a possible approach for patients to limit the use of antihistamines and corticosteroids. There is evidence that allergen immunotherapy can prevent the development of new sensitizations and reduce the risk of later development of asthma in patients with allergic rhinitis. However, some patients do not benefit from this approach and the efficacy of immunotherapy in reducing the severity and relapse of symptoms is still a matter of debate. This review highlights new aspects of allergic rhinitis with a particular focus on the impact of sexual dimorphism on the disease manifestation and efficacy to the allergen specific immunotherapy.

The biological behavior of immune cells is determined by their intrinsic properties and interactions with other cell populations within their microenvironment. Several studies have confirmed the existence of tight spatial interactions between mast cells (MCs) and Tregs in different settings. For instance, we have recently identified the functional cross‐talk between MCs and Tregs, through the OX40L–OX40 axis, as a new mechanism of reciprocal influence. However, there is scant information regarding the single‐cell dynamics of this process. In this study, time‐lapse video microscopy revealed direct interactions between Tregs and MCs in both murine and human cell co‐cultures, resulting in the inhibition of the MC degranulation response. MCs incubated with WT, but not OX40‐deficient, Tregs mediated numerous and long‐lasting interactions and displayed different morphological features lacking the classical signs of exocytosis. MC degranulation and Ca²⁺ mobilization upon activation were inhibited by Tregs on a single‐cell basis, without affecting overall cytokine secretion. Transmission electron microscopy showed ultrastructural evidence of vesicle‐mediated secretion reconcilable with the morphological pattern of piecemeal degranulation. Our results suggest that MC morphological and functional changes following MC–Treg interactions can be ascribed to cell–cell contact and represent a transversal, non‐species‐specific mechanism of immune response regulation. Further research, looking at the molecular composition of this interaction will broaden our understanding of its contribution to immunity.