Reduced IL-10 production by FoxP3+IL-10+ Treg cells is partially compensated by complosome-associated induction of regulatory FoxP3−IL-10+ T cells in allergic eosinophilic asthma

Abstract

Abstract Role of the anti-inflammatory cytokine IL-10 in allergic eosinophilic asthma (AEA) remains controversial, with studies reporting inconsistent findings. Nevertheless, reduced IL-10 production has been described and may contribute to the pathophysiologic features of the disease. Here, we compared FoxP3+IL-10+ Treg cells with the complosome-CD46-induced regulatory FoxP3−IL-10+ T cell capacity to produce IL-10 in AEA. We analyzed CD4+ T cells from 58 adults with controlled AEA and 49 healthy donors using ex vivo phenotypic characterization combined with a defined αCD3/αCD46/IL-2 activation model. CD4+ T cells from patients with controlled AEA showed a predominance of memory CD4+ T cells, reduced frequencies of FoxP3+ Treg cells and increased IFN-γ plasma levels. After CD46-mediated activation in vitro, CD4+FoxP3− T cells from AEA patients exhibited enhanced IFN-γ production together with altered expression of complosome-associated components, including increased CD46 expression and reduced surface C3bIn parallel, reduced frequencies of CD4+FoxP3+ Treg cells with impaired IL-10-producing capacity and normal levels of regulatory FoxP3−IL10+CD49b+ T cells were observed in AEA. The inducible regulatory response within the FoxP3− compartment was primarily driven by increased IL-10 secretion at the single-cell level rather than by an increased frequency of IL-10+ cells. Together, these findings define ex vivo features of complosome-associated CD4+ T cell activation in controlled AEA and indicate that impaired FoxP3+ T cells with diminished IL-10-producing capacity can be partially compensated by complosome-CD46 driven differentiation of CD4+FoxP3− T cells with stronger IL-10 secretion despite overall increase in T1 responses under defined experimental conditions.