Regulatory T Cells in Respiratory Health and Diseases

Figure 1

Potential mechanistic role of Treg function in airway inflammation. (a) An unknown airborne antigen activates dendritic cells. Infiltration of T cells, Th17 (1L-17 production) and Tregs cells at the site, may sometimes cause imbalance in Th17/Treg population. Cytokines like IL-1β and IL-6 may inhibit TGF-β production and can further downregulate Treg activity. (b) Higher TNF-R2 expression mainly due to IL-2 and TNF-α activation is associated with sarcoidosis. ICOS-L on ILC2 engages with ICOS on Tregs enhancing immune regulation. Optimal level of STAT1 within the cell is required for proper regulation of Th1 cells by Treg lymphocytes. Circulating T regs inhibits TH2 cytokine production that otherwise leads to uncontrolled proliferation of pro-inflammatory cell lineages and airway hyperresponsiveness. Increased levels of TGF-β and IL-10 are compatible with increased Tregs. Regulatory T cells also express galectin-9 that can limit the adaptive immune response, in particular, T cell response, while promoting the expansion of regulatory cells. Inflammatory cytokines such as TNF-α and IL-6 can act as a driving factor for the generation of IL-10-producing Tregs through ICOS/ICOS-L interactions. Therapeutic strategy for allergic inflammation that engages MaR1-conditioned Tregs to control ILC2 and CD4+ T cell effector functions. Alternatively, specific regulatory T cells can be suppressed with pleiotropic cytokine Activin-A and acts as a critical controller of allergic airway disease and also suppresses Th responses through regulation of DC function and decreased DC maturation.