Increased expression of IL-1R8 and a possible immunomodulatory role of its ligand IL-37 in allergic rhinitis patients

Allergic rhinitis (AR) is a chronic inflammatory airway disease that is caused by an abnormal T cell response. T helper (Th)-17 cells and Th2 cells are the CD4⁺ T cell subsets implicated in the pathogenesis of AR. The suppression of excessive responses of these Th17 and Th2 cells has been reported to be an effective therapeutic approach to treat AR patients, and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Recent studies have shown that IL-1R8 and its ligand IL-37 negatively regulate the immune response. In this study, we investigated the immunomodulatory the roles of IL-37/IL-1R8 axis in AR patients. We found that IL-1R8 expression was very low on dendritic cells (DCs) and resting CD4⁺ T cells but increased strongly on CD4⁺ T cells following T cell activation. Furthermore, IL-1R8 expression on CD4⁺ T cells was markedly higher in AR patients than in healthy controls. The IL-1R8 ligand IL-37 could act on CD4⁺ T cells to inhibit IL-17 and IL-4 production but could not influence DC-induced IL-17- and IL-4-producing CD4⁺ T cell responses. Meanwhile, recombinant IL-37 (rIL-37) did not influence IL-6, IL-1β, and IL-10 production by DCs and expression of co-stimulatory molecules (including CD80, CD40, CD86 and HLA-DR) in DCs. Thus, IL-37 may regulate aberrant T cell immune response of allergic rhinitis mainly through CD4⁺ T cells, not DCs. The immunomodulatory roles of the IL-37/IL-1R8 axis indicate the therapeutic potential of this axis in AR.