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.
Kubota
Nobuhiko
N
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Ebihara
Takashi
T
Matsumoto
Misako
M
Gando
Satoshi
S
Seya
Tsukasa
T
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D011066:Poly C / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000494:pharmacology; D012367:RNA, Viral / Q000276:immunology*; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; D016898:Interferon-alpha; D015850:Interleukin-6; D011066:Poly C; D012330:RNA, Double-Stranded; D012367:RNA, Viral; C476286:Ticam1 protein, mouse