Immune checkpoint molecules. Possible future therapeutic implications in autoimmune diseases. (November 2019)

• Record Type: Journal Article
• Authors: Huang, Chuan; Zhu, Hao-Xian; Yao, Yuan; Bian, Zhen-Hua; Zheng, Yu-Jian; Li, Liang; Moutsopoulos, Haralampos M.; Gershwin, M. Eric; Lian, Zhe-Xiong
• Is Part Of: Journal of autoimmunity. Volume 104(2019)
• Publication Date: 2019-11
• Subjects: APC antigen presenting cell -- AS ankylosing spondylitis -- BTLA B and T lymphocyte attenuator -- CD Crohn's disease -- CIA collagen induced arthritis -- Con A concanavalin A -- CTLA-4 cytotoxic T-lymphocyte associated antigen 4 -- DC dendritic cell -- EAE experimental autoimmune encephalomyelitis -- Fgl2 fibrinogen like 2 -- GITR glucocorticoid induced TNF receptor -- GWAS Genome-wide association study -- HLA human leukocyte antigen -- IBD inflammatory bowel disease -- ICOS inducible T-cell co-stimulator -- IDO indoleamine 2, 3-dioxygenase -- ILCs innate lymphoid cells -- IMQ Imiquimod -- iNOS inducible Nitric oxide synthase -- ITP immune thrombocytopenia -- LAG-3 lymphocyte-activation gene 3 -- mAb monoclonal antibody -- MG myasthenia gravis -- MHC major histocompatibility class -- MS multiple sclerosis -- PBC primary biliary cholangitis -- PD-1 programmed cell death protein 1 -- pDC plasmacytoid dendritic cell -- SS sjögren's syndrome -- RA rheumatoid arthritis -- SLE systemic lupus erythematosus -- T1D type 1 diabetes -- TCR T cell receptors -- Tfh follicular helper T cells -- TIM-3 T-cell immunoglobulin and mucin-domain containing-3 -- TLR Toll-like receptors -- Treg regulatory T cells -- TIGIT T-cell immunoreceptor with Ig and ITIM domains -- TNFRSF tumor necrosis factor receptor superfamily -- VISTA V domain-containing Ig suppressor of T-cell activation; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2019.102333
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: During host immune response, an initial and sufficient activation is required to avoid infection and cancer, yet an excessive activation bears the risk of autoimmune reactivity and disease development. This fastidious balance of the immune system is regulated by co-stimulatory and co-inhibitory molecules, also known as immune checkpoints. Both excessive co-stimulation and insufficient co-inhibition can induce the activation and proliferation of autoreactive cells that may lead to the development of autoimmune diseases. During the last decade, a growing number of new immune checkpoint receptors and ligands have been discovered, providing an attractive approach to investigate their implication in the pathogenesis of autoimmune diseases and their potential role as targets for effective therapeutic interventions. In this review, we focus on the roles and underlying mechanisms of co-stimulatory and co-inhibitory receptors and other molecules that function as immune checkpoints in autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome, type I diabetes and inflammatory bowel disease. We also summarize previous and current clinical trials targeting these checkpoint pathways in autoimmune diseases and discuss further therapeutic implications and possible risks and challenges. Highlights: Co-stimulatory, co-inhibitory molecules and other molecules function as immune checkpoints keep balance of the immune system. Immune checkpoint molecules participate in preventing or promoting the development of many autoimmune diseases. There are many clinical trails targeting immune checkpoint molecules for treatment of autoimmune diseases. Risks and challenges remain when targeting immune checkpoint molecules for treatment of autoimmune diseases.