IL-6 positively regulates Foxp3+CD8+ T cells in vivo.
Although recent studies have identified regulatory roles for Foxp3(+)CD8(+) T cells, the mechanisms that induce their development and underlie their functions in vivo have not been elucidated. Here, we show that IL-6 positively regulates the Foxp3(+)CD8(+) T-cell development and function. The Foxp3(+)CD8(+) T cells that differentiated in vitro in the presence of IL-6 suppressed autoimmune colitis and arthritis in vivo. Moreover, Foxp3(+)CD8(+) T cells that developed in vivo in the presence of enhanced IL-6 signaling suppressed the development of a spontaneous T(h)17 cell-mediated autoimmune arthritis. Thus, we concluded that Foxp3(+)CD8(+) T cells develop in response to IL-6 and regulate chronic inflammation in T(h)17 cell-mediated F759 autoimmune arthritis. These results suggested that Foxp3(+)CD8(+) T cells may develop in response to IL-6 under certain inflammatory conditions in vivo and may regulate some other chronic inflammation diseases.
Nakagawa
Takayuki
T
Laboratory of Developmental Immunology and CREST Program of Japan Science and Technology Agency, Graduate School of Frontier Biosciences, Graduate School of Medicine and WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
Tsuruoka
Mineko
M
Ogura
Hideki
H
Okuyama
Yuko
Y
Arima
Yasunobu
Y
Hirano
Toshio
T
Murakami
Masaaki
M
D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000517:prevention & control; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors
D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C494199:IL6ST protein, human; C508018:Il2ra protein, mouse; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; C499308:Rag2 protein, mouse; D050822:Cytokine Receptor gp130