Regulatory T cells in many flavors control asthma.
That regulatory T cells (Tregs) have a crucial role in controlling allergic diseases such as asthma is now undisputed. The cytokines most commonly implicated in Treg-mediated suppression of allergic asthma are transforming growth factor-beta (TGF-beta) and interleukin (IL)-10). In addition to naturally occurring Tregs, adaptive Tregs, induced in response to foreign antigens, have been shown in recent studies. The concept of inducible/adaptive Tregs (iTregs) has considerable significance in preventing asthma if generated early enough in life. This is because cytokines such as IL-4 and IL-6 inhibit Foxp3 induction in naive CD4+ T cells and therefore de novo generation of Tregs can be expected to be less efficient when it is concomitant with effector cell development in response to an allergen. However, if iTregs can be induced, the process of infectious tolerance would facilitate expansion of the iTreg pool as suggested in the recent literature. It is tempting to speculate that there is a window of opportunity in early life in the context of a relatively immature immune system that is permissive for the generation of iTregs specific to a spectrum of allergens that would regulate asthma for lifelong. The focus of this review is the relevance of nTregs and iTregs in controlling asthma from early life into adulthood, the mechanisms underlying Treg function, and the prospects for using our current concepts to harness the full potential of Tregs to limit disease development and progression.
Ray
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A
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. raya@pitt.edu
Khare
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A
Krishnamoorthy
N
N
Qi
Z
Z
Ray
P
P
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology
D000485:Allergens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4