Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach

被引:0
作者
Yoshiya Tanaka
Yiming Luo
John J. O’Shea
Shingo Nakayamada
机构
[1] University of Occupational and Environmental Health,The First Department of Internal Medicine, School of Medicine
[2] Japan,Vasculitis Translational Research Program Systemic Autoimmunity Branch
[3] National Institute of Arthritis,Molecular Immunology & Inflammation Branch, and Translational Immunology Section
[4] Musculoskeletal,undefined
[5] and Skin Diseases NIH,undefined
[6] National Institute of Arthritis & Musculoskeletal and Skin Diseases,undefined
[7] NIH,undefined
来源
Nature Reviews Rheumatology | 2022年 / 18卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
The four Janus kinase (JAK) proteins and seven signal transducer and activator of transcription (STAT) transcription factors mediate intracellular signal transduction downstream of cytokine receptors, which are implicated in the pathology of autoimmune, allergic and inflammatory diseases. Development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders. JAK inhibitors suppress intracellular signalling mediated by multiple cytokines involved in the pathological processes of rheumatoid arthritis and many other immune and inflammatory diseases, and therefore have the capacity to target multiple aspects of those diseases. In addition to rheumatoid arthritis, JAK inhibition has potential for treatment of autoimmune diseases including systemic lupus erythematosus, spondyloarthritis, inflammatory bowel disease and alopecia areata, in which stimulation of innate immunity activates adaptive immunity, leading to generation of autoreactive T cells and activation and differentiation of B cells. JAK inhibitors are also effective in the treatment of allergic disorders, such as atopic dermatitis, and can even be used for the COVID-19-related cytokine storm. Mechanism-based treatments targeting JAK–STAT pathways have the potential to provide positive outcomes by minimizing the use of glucocorticoids and/or non-specific immunosuppressants in the treatment of systemic immune-mediated inflammatory diseases.
引用
收藏
页码:133 / 145
页数:12
相关论文
共 127 条
[1]  
Smolen JS(2018)Rheumatoid arthritis Nat. Rev. Dis. Prim. 8 18001-8
[2]  
Tanaka Y(2020)Rheumatoid arthritis Inflamm. Regen. 40 1-699
[3]  
Smolen JS(2020)EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update Ann. Rheum. Dis. 79 685-68
[4]  
Macchi P(1995)Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID) Nature 377 65-153
[5]  
Johnston JA(1994)Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2 Nature 370 151-i74
[6]  
Tanaka Y(2012)In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis Ann. Rheum. Dis. 71 i70-170
[7]  
O’Shea JJ(2012)JAKs and STATs in immunity, immunodeficiency, and cancer N. Engl. J. Med. 368 161-ii115
[8]  
O’Shea JJ(2013)Janus kinase inhibitors in autoimmune diseases Ann. Rheum. Dis. 72 ii111-i3
[9]  
Kontzias A(2019)The JAK inhibitors: do they bring a paradigm shift for the management of rheumatic diseases? Rheumatology 58 i1-962
[10]  
Yamaoka K(2019)Clinical significance of Janus kinase inhibitor selectivity Rheumatology 58 953-2020