Jones, Simon - Cardiff University

个人简介

I am a leading inflammation researcher and Arthritis Research UK Programme Grant holder at Cardiff University. With a primary interest in inflammatory cytokines I aim to understand the mechanisms that affect the balance between competent host immunity and inflammation-induced tissue injury, and how the cytokine network shapes the course of disease in patients. Since 1999, my laboratory has focused on the biology of cytokines that trigger responses through the latent transcription factors Signal Transducers and Activators of Transcription (STAT)-1 and STAT3. My work on the cytokines interleukin (IL)-6, IL-10, IL-27 and interferon (IFN)-g explain how cytokine networks established as a response to infection, trauma or injury combine to promote protective immunity or drive transition to pathological immunity. Publications in The Journal of Experimental Medicine (Jones et al., 1999), Immunity (Hurst et al., 2001), The Journal of Clinical Investigation (McLoughlin et al., 2003) and PNAS (McLoughlin et al., 2005) were amongst the first to report the physiological importance of IL-6 acting through its soluble receptor (termed IL-6 trans-signaling) in disease. This required development of novel in vivo approaches and the application of soluble gp130 as the natural inhibitor of IL-6 trans-signaling. Specifically, my studies in inflammatory arthritis have supported the translational development of soluble gp130 as a therapeutic modality (FE999301 – in clinical trials with Ferring Pharmaceuticals) for the treatment of human disease (Nowell, et al., 2003, 2009). These observations also explain therapeutic action of other IL-6-directed biological drugs (e.g., tocilizumab, olokizumab, sarilumab and sirukumab), which are in late stage clinical development or routine clinical practice. I am a leading expert in this area as evidence by a series of high-profile review articles on this subject (e.g., Hunter & Jones, Nature Immunology 16:448 2015; Jones et al., Journal of Clinical Investigation 121:3375 2011), and I am included on various advisory boards for pharmaceutical companies. More recently, I have explored the signaling cassette responsible for the cytokine control of disease progression. For example, studies published in The Journal of Immunology (Nowell et al., 2009; Jones et al., 2010), Annals of Rheumatic Disease (Jones et al., 2013) and Immunity (Fielding et al., 2014) describe how changes in the relative activation of STAT1 or STAT3 elicit profound differences in disease outcome. This research has an immediate impact on patient stratification and clinical decisions relating to the best course of therapy. For example, my recent publication in the Journal of Experimental Medicine (Jones et al., 2015) describes a mechanism that accounts for the development of a type of rheumatoid arthritis that is both severe in nature and challenging to treat. My research is therefore contributing to improvements in patient diagnosis, stratification and treatment decisions.

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Jones, S. A. 2017. On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity 46(1), pp. 133-147. (10.1016/j.immuni.2016.12.010) pdf Clement, M.et al. 2016. Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. PLoS Pathogens 12(12), article number: e1006050. (10.1371/journal.ppat.1006050) pdf Perks, W.et al. 2016. Death Receptor 3 promotes chemokine directed leukocyte recruitment in acute resolving inflammation and is essential for pathological development of mesothelial fibrosis in chronic disease. American Journal of Pathology 186(11), pp. 2813-2823. (10.1016/j.ajpath.2016.07.021) pdf Jones, G., Hill, D. and Jones, S. 2016. Understanding immune cells in tertiary lymphoid organ development: it is all starting to come together. Frontiers in Immunology 7, pp. 1-13., article number: 401. (10.3389/fimmu.2016.00401) pdf Liao, C.et al. 2016. IL-10 differentially controls the infiltration of inflammatory macrophages and antigen-presenting cells during inflammation. European Journal of Immunology 46(9), pp. 2222-2232. (10.1002/eji.201646528) pdf Davies, R.et al. 2016. Serum Vascular Cell Adhesion Molecule 1 levels are associated with vascular Dysfunction and increased cardiovascular risk in an animal model and patients with Rheumatoid Arthritis. Rheumatology 55(Supp 1), pp. 54-54. (10.1093/rheumatology/kew102.004) Harvey, A.et al. 2016. Novel application of behavioral assays allows dissociation of joint pathology from systemic extra-articular alterations induced by inflammatory arthritis. Journal of Rheumatic Diseases and Treatment 2(1), article number: 033. pdf Jones, G. W. and Jones, S. A. 2016. Ectopic lymphoid follicles: inducible centres for generating antigen-specific immune responses within tissues. Immunology 147(2), pp. 141-151. (10.1111/imm.12554) pdf Lacroix, M.et al. 2015. Novel insights into IL-6 cis- and trans-signaling pathways by differentially manipulating the assembly of the IL-6 signaling complex. Journal of Biological Chemistry 290, pp. 26943-26953. (10.1074/jbc.M115.682138) Jones, G.et al. 2015. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. Journal of Experimental Medicine 212(11), pp. 1793-1802. (10.1084/jem.20132307) pdf