Subsets of regulatory T cells and their roles in allergy

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.

Figure 1

Cell signaling pathways of Tregs. TGF-β = transforming growth factor beta; TGF-βR = transforming growth factor beta receptor; RA = retinoic acid; RAR = retinoic acid receptor; TCR = T cell receptor; IL = interleukin; ILR = interleukin receptor; Smad = small body size and mothers against decapentaplegic; ERK = extracellular regulated protein kinase; Jnk = Jun N-terminal kinase; PLCγ = phospholipase C gamma; PKC = protein kinase C; TAK = TGF beta activated kinase; NFkB = nuclear factor kappa B; PI3K = phosphoinositide 3 kinase; AKT = protein kinase B; JAK = Janus-family tyrosine kinase; STAT = signal transducer and activator of transcription; T bet = T cell specific T-box transcription factor; Bcl-2 = B cell leukemia 2 protein; Foxp3 = forkhead box P3; CNS = non-coding sequence.

Figure 2

Influence of Tregs on other cell types. Th = helper T cells; iTreg = inducible/adaptive regulatory T cell.