Contributions of innate lymphocytes to allergic responses

Abstract

Purpose of review: Allergic diseases represent a growing global health concern, especially among pediatric populations. Current strategies for the treatment of allergies and asthma focus on limiting the severity of the symptoms; however, additional research investigating the mechanisms promoting inflammation in the context of allergic reactions may lead to the development of more effective therapeutic strategies.

Recent findings: Novel studies have highlighted the contributions of innate lymphocytes to the induction of inflammatory responses to allergens. Remarkably, neuron-derived signals, hormones, and even vitamins have been suggested to modulate the activity of innate lymphocytes, opening new windows of opportunity for the treatment of allergic inflammation.

Summary: These studies highlight the complex interactions of the nervous, endocrine, and immune system that promote pathology in the context of allergic inflammation. Further studies are required to understand these interactions in order to aid in the development of novel and much-needed therapies to treat allergic conditions.

Figure 1.. Regulators of ILC2-mediated allergic inflammation.

ILC2s are critical mediators of allergic inflammation that are activated in response to cytokines (IL-4, IL-25, IL-33) and inflammatory mediators such as prostaglandins and cysteinyl leukotrienes (Cys-Lkt), free fatty acids (OA and LA), complement proteins (C3a),and neuron-derived signals (NMU, CGRP, GABA). Further, it has also been demonstrated that ILC2s can be negatively regulated by β₂AR agonists, β7nAChR agonists, Vitamin A, and testosterone. Gaining a better understanding of positive and negative regulators of ILC2 responses may inform new strategies to treat allergic inflammation. OA: oleic acid, LA: linoleic acid. NMU: neuromedin U. CGRP: Calcitonin gene-related peptide. GABA: gamma-aminobutyric acid

Fig 2.. Innate sources of IL-17 in allergic responses.

Recent research has demonstrated that exposure to allergens, in conjunction with exposure to fungal-derived signals results in robust type 17-mediated cytokine responses characterized by the accumulation of neutrophils and T_H17 cells. Different innate immune cells have been reported to contribute to the early secretion of IL-17 in response to allergic exposure including dermal γδ T cells, epithelial cells, eosinophils, NK cells, and a subset of ILC2s. Further studies are required to define the contributions of these cells to the pathology associated with allergies and asthma.