IL-6 and IFN-alpha from dsRNA-stimulated dendritic cells control expansion of regulatory T cells.

Foxp3(+)CD4(+) regulatory T cells (Treg) control not only autoimmunity but also the effective immune response against RNA virus infections, which produces virus-derived double-stranded RNA (dsRNA). To induce effective anti-viral immunity, it is a key issue to learn how Treg respond to dsRNA in vitro and in vivo. We here showed that synthetic dsRNA, polyI:C, caused peripheral expansion of functional Treg in a TICAM-1- and IL-6-dependent manner in vivo. PolyI:C did not expand Treg directly, but promoted the expansion of naturally occurring Treg indirectly through IL-6 produced from dendritic cells (DCs). In addition, the expansion of Treg by IL-6 was inhibited by IFN-alpha from polyI:C-stimulated DCs. These data suggest that the balance of IL-6 and IFN-alpha in the region of RNA virus infection may determine the number of peripheral Treg, which affects the effective immune responses against viruses.