Jonathan H. Esensten, MD, PhD, Yannick D. Muller, MD, PhD, Jeffrey A

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Presentation transcript:

Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontier Jonathan H. Esensten, MD, PhD, Yannick D. Muller, MD, PhD, Jeffrey A. Bluestone, PhD, Qizhi Tang, PhD Journal of Allergy and Clinical Immunology Volume 142, Issue 6, Pages 1710-1718 (December 2018) DOI: 10.1016/j.jaci.2018.10.015 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Treg cell mechanisms of action. Treg cells control inflammation and effector T-cell function through a variety of mechanisms both in lymph nodes and tissues. Treg cells mirror the phenotype of the effector cells that they regulate. In addition to controlling effector T-cell function, Treg cells contribute to tissue repair. Journal of Allergy and Clinical Immunology 2018 142, 1710-1718DOI: (10.1016/j.jaci.2018.10.015) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Ongoing Treg cell clinical trials. Clinical trials involving Treg cell therapy were identified on clinicaltrials.gov and categorized by location (A) and by clinical indication (B). Data were collected in August 2018. AD, Autoimmune disease; HSCT, hematopoietic stem cell transplantation; SOT, solid organ transplantation. Journal of Allergy and Clinical Immunology 2018 142, 1710-1718DOI: (10.1016/j.jaci.2018.10.015) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Potential future applications of Treg cells to target specific tissues and diseases. Therapeutic Treg cell products could be differentiated to suppress specific inflammatory T-cell subsets. Treg cells can be engineered further to traffic to diseased tissue through expression of specific antigen receptors. In conferring antigen specificity, we note that the suppressive activity of Treg cells in lymph nodes would more likely involve TCRs targeting specific antigens, whereas CARs might be more effective in tissues. Taken together, these approaches might be sufficient to target specific tissues or organs and treat a variety of autoimmune and autoinflammatory diseases. ALS, Amytrophic lateral sclerosis; APC, antigen-presenting cell; CAR, chimeric antigen receptor; CTL, cytotoxic T cells; Mph, macrophage; MS, multiple sclerosis; NK, natural killer cells; RA, rheumatoid arthritis; T1D, type 1 diabetes mellitus; Tfh, follicular helper T cells; Tfr, follicular regulatory T cells. Journal of Allergy and Clinical Immunology 2018 142, 1710-1718DOI: (10.1016/j.jaci.2018.10.015) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions