ROCKing cytokine secretion balance in human T cells |
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| Affiliation: | 1. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;2. Division of Translational Research, Clinical and Translational Research Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;3. Department of Pulmonary Medicine, Saitama City Hospital, 2460 Mimuro, Midori-ku, Saitama City, Saitama 336-8522, Japan;4. Department of Pulmonary Medicine, Tokyo Saiseikai Central Hospital, 1-4-17, Mita, Minato-ku, Tokyo 108-0073, Japan;5. Department of Pulmonary Medicine, Kawasaki Municipal Ida Hospital, 2-27-1, Ida, Nakahara-ku, Kawasaki-shi, Kanagawa 211-0035, Japan;6. Division of Pulmonary Medicine, Department of Internal Medicine, Federation of National Public Service Personnel Mutual Aid Associations, Tachikawa Hospital, 4-2-22, Nishiki-cho, Tachikawa-shi, Tokyo 190-8531, Japan;7. Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, 2-5-1, Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan;8. Department of Internal Medicine, Saitama Medical Center, 4-9-3, Kitaurawa, Urawa-ku, Saitama-shi, Saitama 330-0074, Japan;9. Department of Respiratory Medicine, Tokyo Dental College Ichikawa General Hospital, 5-11-13, Sugano, Ichikawa-shi, Chiba, Japan Chiba 272-0824, Japan;10. Department of Medicine, Kitasato University Kitasato Institute Hospital, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8642, Japan;11. Department of Internal Medicine, Keiyu Hospital, 3-7-3, Minatomirai, Nishi-ku, Yokohama-shi, Kanagawa 220-8521, Japan;12. Department of Internal Medicine, Nihon Koukan Hospital, 1-2-1, Koukan-douri, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-0852, Japan;13. Department of Internal Medicine, Hino Municipal Hospital, 4-3-1, Tamadaira, Hino-shi, Tokyo 191-0062, Japan;14. Sano Kousei General Hospital, 1728 Horigome-cho, Sano-shi, Tochigi 327-8511, Japan;15. Pulmonary Division, Department Internal Medicine, Saiseikai Utsunomiya Hospital, 911-1, Takebayashi-machi, Utsunomiya-shi, Tochigi 321-0974, Japan;p. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 11S261, Bethesda, MD 20814, USA;q. Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan |
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| Abstract: | Balanced regulation of cytokine secretion in T cells is critical for maintenance of immune homeostasis and prevention of autoimmunity. The Rho-associated kinase (ROCK) 2 signaling pathway was previously shown to be involved in controlling of cellular movement and shape. However, recent work from our group and others has demonstrated a new and important role of ROCK2 in regulating cytokine secretion in T cells. We found that ROCK2 promotes pro-inflammatory cytokines such as IL-17 and IL-21, whereas IL-2 and IL-10 secretion are negatively regulated by ROCK2 under Th17-skewing activation. Also, in disease, but not in steady state conditions, ROCK2 contributes to regulation of IFN-γ secretion in T cells from rheumatoid arthritis patients. Thus, ROCK2 signaling is a key pathway in modulation of T-cell mediated immune responses underscoring the therapeutic potential of targeted inhibition of ROCK2 in autoimmunity. |
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| Keywords: | Human T cells Pro-inflammatory cytokines IL-2 IL-10 STAT3 |
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