Regulatory T Cells in Asthma Clare M. Lloyd, Catherine M. Hawrylowicz  Immunity  Volume 31, Issue 3, Pages 438-449 (September 2009) DOI: 10.1016/j.immuni.2009.08.007 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Regulatory Pathways Maintain Lung Homeostasis The lung is maintained in a state of homeostasis by a complex network of cells and molecules. IL-10 plays a central role in this process, but the role of TGF-β is less clear at present. Exposure of susceptible individuals to allergen is associated with a Th2 cell type immune response characterized by IL-4, IL-5, IL-13, and TNF, which culminates in leukocyte infiltration of the lungs. The development of this inflammation is influenced by multiple factors, but early childhood infection, diet, vitamin D, and TLR ligand expression all affect the initiation and development of the allergic response. In a proportion of individuals, inflammation is chronic and associated with significant remodeling of the airways. IL-10 and TGF-β are thought to be able to promote resolution of inflammation whereas TFG-β family members initiate tissue repair and remodeling. Induction of TGF-β by Th2 cytokines during acute inflammation may also contribute to lung remodeling. Whether chronic asthma develops as a result of ineffective inflammatory resolution or as an aberrant wound healing response is the subject of investigation, but it is likely that IL-10 and TGF-β are key mediators. Immunity 2009 31, 438-449DOI: (10.1016/j.immuni.2009.08.007) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 2 Effect of Current Asthma Treatments on Regulatory Pathways Regulatory T cells inhibit effector T cells, antigen-presenting cells, and cells of the innate immune response associated with the asthmatic reaction. Corticosteroids, a key treatment for asthma, are associated with the upregulation of both Foxp3+ Treg cells and IL-10 production by CD4+ T cells. Allergen immunotherapy has also been associated with an increase in allergen-specific IL-10-secreting Treg cells. More recent data suggest that Foxp3+ Treg cells may also be increased by this treatment. Vitamin D may both directly increase IL-10 and also enhance steroid-induced IL-10 production. Both Foxp3+ and IL-10+ (Foxp3-negative and -positive) Treg cell populations are likely to use additional inhibitory mechanisms including cell-contact-dependent pathways and cytotoxicity. Immunity 2009 31, 438-449DOI: (10.1016/j.immuni.2009.08.007) Copyright © 2009 Elsevier Inc. Terms and Conditions