Introduction
Subset | Specific marker | Secretory products | Actions | Location |
---|---|---|---|---|
nTreg | CD4, CD25, Foxp3 | IL-10, TGF-β | Block T cell proliferation, suppression of DCs, inhibition of effector Th1, Th2, and Th17 cells; eliminate production of allergen-specific IgE, induce IgG4 secretion; suppress mast cells, basophils, and eosinophils; interact with resident tissue cells and participate tissue remodeling [12] | Thymus [9] |
ICOS(+) Treg | CD4, CD25, Foxp3, ICOS | IL-10, IL-17, IFN-γ | Suppress hapten-reactive CD8(+) T cells [15] | Generated from nTregs |
iTreg | CD4, Foxp3 | IL-10, TGF-β | Similar to nTreg [16] | Periphery |
Tr1 | CD4, CD25 | IL-10 | Generated from non-Treg cell precursors and home lungs and draining lymph nodes [18] | |
CD8(+)Treg | CD8, Foxp3, CD25 (not for tonsil origin), CD28 | IL-10, TNF-α, IFN-γ, GB | Generated from OT-1 CD8 cells [9]and tonsils | |
IL-17-producing Foxp3 (+) Treg | CD4, Foxp3,CCR6,RORGTF | IL-17 | Inhibit the proliferation of CD4(+) effector T cells [10]. | Differentiated from CD4(+)Foxp3(+)CCR6(-) Tregs in peripheral blood and lymphoid tissue [10] |
Subsets of Tregs
nTregs
iTregs
Tr1 cells
CD8 + Tregs
IL-17-producing Foxp3+ Tregs
Cell signaling of Tregs and potential mechanisms of their actions
Cell signaling of Tregs
Potential mechanisms of their actions
Actions of Tregs on other immune cells
Tregs and mast cells
Tregs and Th cells
Tregs and DCs
Tregs and eosinophils
Tregs and Bregs
Contribution of Tregs to allergy
Disease | Location | Involvement of Tregs |
---|---|---|
Allergic dermatitis | Skin, the secondary lymphoid organs | The depletion of Tregs leads to significantly exacerbated skin inflammation, as well as elevated serum IgE levels [50]. |
Allergic rhinitis | Tonsil, Blood | |
Allergic airway inflammation | Blood, peribronchial lymph nodes | Foxp3 expression is reduced and CD25(hi) Treg-suppressive function is deficient in asthma. Corticosteroids and allergen immunotherapy act on Tregs, in part to increase IL-10 production, while vitamin D3 and long-acting beta-agonists enhance Tr1 cell function [57]. Heligmosomoides polygyrus infection is associated with elevated numbers of Tregs in airway challenged mice [60], efficiently protects mice from asthma by induction of accumulation of highly suppressive Tregs in the lungs [61]. |
Tregs in allergic dermatitis
Tregs in allergic rhinitis
Tregs in allergic lower airway inflammation
Roles of Tregs in treatment of allergy
Therapy | Action of Tregs |
---|---|
SIT | Suppression of T cell responses to the T-cell epitopes of major allergens. Autocrine action of IL-10 and/or TGF-β, which are produced by antigen-specific Tregs. They may suppress IgE production and induce IgG4 and IgA production against allergens [65]. Histamine released from mast cells and basophils may efficiently contribute to immunoregulation, and affect Tregs [6]. Der p immunotherapy causes increased number of Treg cells, and elevated IL-10 production. IL-10(+) Tregs may respond to Der p-2 and down-regulate NF-κB/p65 expression in PBMC to maintain immune tolerance during SIT [66]. |
SLIT | Allergen extracts administered via the sublingual route are long retained at mucosal level, where the allergen molecules are captured by DCs, following their migration in the draining lymph nodes, presented to T cells to generate iTregs [64]. SLIT causes the absence of effectors cells, such as mast cells, basophils and eosinophils in the oral mucosa of allergic subjects. Skewing of allergic-specific effector T cells to a Tr1 phenotype appears to be a critical event in successful allergen-specific immunotherapy and glucocorticoids and beta2-agonists treatment [8]. |
Bacteria therapy | Lactobacilli prime of DCs to drive the development of Tregs. These Tregs produce increased IL-10 inhibiting the proliferation of bystander T cells [4]. |
Treg therapy | Transfer of OVA peptide-specific CD4 + CD25+ Tregs to OVA-sensitized mice reduces AHR, recruitment of eosinophils, and Th2 cytokine expression in the lung after allergen challenge [70]. |