title: ROCKing cytokine secretion balance in human T cells.
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.
authors: Kadmon Research Institute, New York, NY 10016, United States. Electronic address: Alexandra.Zanin-Zhorov@kadmon.com.
authors: Alexandra
authors: A
authors: Zanin-Zhorov
authors: Kadmon Research Institute, New York, NY 10016, United States.
authors: Samuel D
authors: SD
authors: Waksal
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D058408:Th1-Th2 Balance; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D007378:Interleukins; D007371:Interferon-gamma; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D000098546:Interleukin-21
keywords: Human T cells; IL-10; IL-2; Pro-inflammatory cytokines; STAT3