Subsets of regulatory T cells and their roles in allergy
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REVIEW
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Subsets of regulatory T cells and their roles in allergy Huiyun Zhang1,2†, Hui Kong3†, Xiaoning Zeng3, Lianyi Guo1, Xiaoyun Sun1 and Shaoheng He1*
Abstract In recent years, it is recognized that acquired immunity is controlled by regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy are mainly caused by hyperresponsiveness of immune system to allergens that acquires after birth, Tregs likely play key roles in the pathogenesis of allergy, particularly during the sensitization phase. However, accumulated information indicate that there are several distinctive subtypes of Tregs in man, and each of them seems to play different role in controlling immune system, which complicates the involvement of Tregs in allergy. The aim of the present study is to attempt to classify subtypes of Tregs and summarize their roles in allergy. Tregs should include natural Tregs (nTreg) including inducible costimulator (ICOS)(+) Tregs, inducible/ adaptive Tregs (iTreg), interleukin (IL)-10-producing type 1 Tregs (Tr1 cells), CD8(+) Tregs and IL-17-producing Tregs. These cells share some common features including expression of Foxp3 (except for Tr1 cells), and secretion of inhibitory cytokine IL-10 and/or TGF-β. Furthermore, it is noticeable that Tregs likely contribute to allergic disorders such as dermatitis and airway inflammation, and play a crucial role in the treatment of allergy through their actions on suppression of effector T cells and inhibition of activation of mast cells and basophils. Modulation of functions of Tregs may provide a novel strategy to prevent and treat allergic diseases. Keywords: Regulatory T cell, Allergy, IL-10, TGF-β, Mast cell
Introduction Allergic diseases are major diseases involving approximately 22% world population [1]. The diseases include allergic rhinitis, allergic asthma, allergic dermatitis, allergic conjunctitis, anaphylaxis, food or drug allergic reactions etc. It has long been accepted that allergic inflammation is the fundamental pathological changes of allergy, and type I hypersensitivity of immune system is the basic mechanism of allergic inflammation [2]. There are two phases in the basic process of IgE mediated allergic inflammation, the sensitization phase and effection phase. It has long been recognized that lymphocytes guide (if not dictate) the sensitization of allergy by directing differentiation of uncommitted (naive) CD4 (+) T helper (Th) cells towards Th1, Th2, Th17 and Treg phenotypes. For example, the presence of IL-12 in the local
* Correspondence: [email protected] † Equal contributors 1 Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning 121001, People’s Republic of China Full list of author information is available at the end of the article
milieu skews towards Th1 [expression of T box expressed in T cells (T-bet)], IL-4 towards Th2 (expression of GATA-3), transforming growth factor (TGF)-β toward
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