The regulation of regulation: interleukin-10 increases CD4+ CD25+ regulatory T cells but impairs their immunosuppressive activity in murine models with schistosomiasis japonica or asthma.

CD4+ CD25+ Foxp3+ regulatory T (Treg) cells play an important role in maintaining immune homeostasis. Interleukin-10 (IL-10), a cytokine with anti-inflammatory capacities, also has a critical role in controlling immune responses. In addition, it is well known that production of IL-10 is one of the suppression mechanisms of Treg cells. However, the action of IL-10 on Treg cells themselves remains insufficiently understood. In this study, by using a Schistosoma japonicum-infected murine model, we show that the elevated IL-10 contributed to Treg cell induction but impaired their immunosuppressive function. Our investigations further suggest that this may relate to the up-regulation of serum transforming growth factor (TGF-β) level but the decrease in membrane-bound TGF-β of Treg cells by IL-10 during S. japonicum infection. In addition, similar IL-10-mediated regulation on Treg cells was also confirmed in the murine model of asthma. In general, our findings identify a previously unrecognized opposing regulation of IL-10 on Treg cells and provide a deep insight into the precise regulation in immune responses.