The immune system projects a complex interplay between the host's genetic composition and environmental factors. Any irregularities, even subtle ones, could lead to out of proportion immune responses. Among defects, allergies and hypersensitivities are increasingly prevalent in both developed and developing countries, with limited therapeutic tools that mainly focus on the relief of the symptoms. One of the common inherent hypersensitivities is atopy and is a condition in which a tendency to immunoglobulin E (IgE) overproduction against the small amounts of foreign antigens is present (1). Atopic diseases are the clinical presentations of the atopy and encompass allergic rhinitis, asthma, food allergies, and atopic dermatitis. Despite being related terms, atopy and allergy are two distinct entities. The term allergy refers to the development of symptoms upon contact with the allergen of which there is an IgE-specific response previously, while individuals with atopy may remain clinically silent in the form of asymptomatic sensitization. According to recent estimates, the highest rates of allergic diseases worldwide belong to asthma, food allergies, drug allergies, and allergic rhinitis (2).
The various lineage of cells contribute to the pathophysiology of atopy and allergic diseases; however, there is a central role for T helper 2 (Th2) lymphocyte and its related cytokines, including Interleukin (IL)-4, IL-5, and IL-13. These elements provoke a cascade of sensitization mediated by the production of IgE. Induction of Th2 transformation to the naïve T cells initiates with allergen recognition by antigen-presenting cells (APCs) that migrate to the nearby lymph nodes. Th2 cells then activate the B cells responsible for differentiation into the allergen-specific IgE-producing plasma cells. The tissue-resident mast cells and basophils receive allergen-specific IgE by their high-affinity IgE receptor labeled FcεRI. By the next entry of the allergen, this machinery responds by producing numerous mediators, including histamine, prostaglandins, leukotrienes, chemokines, reactive oxygen species (ROS), and recruitment eosinophils with their tissue-destructing granules. These reactions contribute to allergic manifestations, including tissue edema, vasodilation, and bronchospasm (3).
While inflammatory cells are the actors of the hypersensitivity responses, the cytokines released by these cells have gained attraction in recent studies as they might influence vulnerability to atopic diseases. Moreover, the solid hereditary background has been attributed to atopic diseases, including atopic dermatitis and allergic rhinitis (4, 5). Thus, exploring the polymorphisms in genes modulating cytokine expression, specifically interleukins, is essential for the surveillance of susceptible individuals.
The mainstream studies on the association of Interleukins gene polymorphisms and atopy are around direct mediators, including IL-4 and IL-13 (6–12). However, other alterations of genes expressing ILs and their receptors have been investigated in parallel.
One of the ILs responsible for proliferation and regulating the homeostasis of T cells is IL-7 (13). It is secreted by various non-hematopoietic cells, including keratinocytes, epithelial cells in the intestine, prostate, and thymus, and dendritic cells (DCs) (14–16). IL-7 is essential for maintaining the survival of both naïve and mature T cells through its receptor, IL-7R, which has a common chain with thymic stromal lymphopoietin (TSLP) (17). These imply that IL-7 may have a regulatory effect on the central orchestrator of atopy, the Th2 cell. Thus, seeking the SNPs and polymorphisms of the IL-7 and IL-7R genes seems worthwhile (18, 19). Moreover, the possible role of IL-7 in atopy was suggested when the results of the allergen patch test showed that the expression of IL-7 messenger RNA was high in atopic dermatitis patients (20, 21).
In this study, we aimed to evaluate the genetic associations of IL7R gene SNPs and atopy in addition to the measurement of IL-7 serum levels in atopic patients.