Immune Modulation of Monocytes Dampens the IL-17 + γδ T Cell Response and Associated Psoriasis Pathology in Mice.

Autor:	Pinget GV; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia., Tan J; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia; Human Health, Nuclear Science & Technology and Landmark Infrastructure (NSTLI), Australian Nuclear Science and Technology Organisation, Sydney, New South Wales, Australia., Niewold P; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia., Mazur E; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia., Angelatos AS; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia., King NJC; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia; Sydney Cytometry, The University of Sydney and The Centenary Institute, Camperdown, New South Wales, Australia., Macia L; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: laurence.macia@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2020 Dec; Vol. 140 (12), pp. 2398-2407.e1. Date of Electronic Publication: 2020 May 07.
DOI:	10.1016/j.jid.2020.03.973
Abstrakt:	Psoriasis is a chronic inflammatory autoimmune skin condition that affects millions of people worldwide. It is driven by IL-17-producing CD4 and γδ T cells and targeted by current anti-IL-17 or anti-IL-23 mAb therapies. These treatments are expensive, increase the risk of opportunistic infections, and do not specifically target the inflammatory cascade. Other cells, including inflammatory monocytes, have been shown to migrate to psoriatic plaques in both human disease and the imiquimod-induced mouse model and could thus constitute potential alternative therapeutic targets. In the mouse, immune modifying particles (IMPs) specifically target Ly6C hi inflammatory monocytes migrating to the site of inflammation, sequestering them in the spleen. In this project, we determined whether IMPs could mitigate the development of imiquimod -induced psoriasis in mice. IMP treatment significantly reduced imiquimod-induced psoriasis severity, decreasing dermal infiltration of Ly6C hi monocytes as well as early-stage monocyte-derived dermal macrophages. This was associated with reduced levels of hallmark cytokines IL-23 and IL-1β as well as associated IL-17-producing γδ T cells. Our work highlights the crucial importance of inflammatory monocytes in the development of this disease as well as a therapeutic potential for IMP in psoriasis. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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