IL-6 positively regulates Foxp3+CD8+ T cells in vivo

Takayuki Nakagawa; Mineko Tsuruoka; Hideki Ogura; Yuko Okuyama; Yasunobu Arima; Toshio Hirano; Masaaki Murakami

doi:10.1093/intimm/dxp119

IL-6 positively regulates Foxp3+CD8+ T cells in vivo

Int Immunol. 2010 Feb;22(2):129-39. doi: 10.1093/intimm/dxp119. Epub 2009 Dec 30.

Authors

Takayuki Nakagawa¹, Mineko Tsuruoka, Hideki Ogura, Yuko Okuyama, Yasunobu Arima, Toshio Hirano, Masaaki Murakami

Affiliation

¹ 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.

PMID: 20042455
DOI: 10.1093/intimm/dxp119

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arthritis / immunology
Arthritis / prevention & control
Autoimmune Diseases / immunology
Autoimmune Diseases / prevention & control
CD8 Antigens / genetics
CD8 Antigens / metabolism*
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / transplantation
Cell Differentiation
Cell Proliferation
Cells, Cultured
Colitis / immunology
Colitis / prevention & control
Cytokine Receptor gp130 / genetics
Cytokine Receptor gp130 / metabolism
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics
Disease Models, Animal
Forkhead Transcription Factors / deficiency
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism*
Humans
Inflammation Mediators / metabolism
Interleukin-2 Receptor alpha Subunit / metabolism
Interleukin-6 / deficiency
Interleukin-6 / genetics
Interleukin-6 / metabolism*
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Signal Transduction*
T-Lymphocytes, Helper-Inducer / immunology
Time Factors

Substances

CD8 Antigens
DNA-Binding Proteins
Forkhead Transcription Factors
Foxp3 protein, mouse
IL6ST protein, human
Il2ra protein, mouse
Inflammation Mediators
Interleukin-2 Receptor alpha Subunit
Interleukin-6
Rag2 protein, mouse
Cytokine Receptor gp130