S100A8/A9-alarmin promotes local myeloid-derived suppressor cell activation restricting severe autoimmune arthritis.

Autor:	von Wulffen M; Institute of Immunology, University of Münster, Münster, Germany; Interdisciplinary Center of Clinical Research (IZKF), University of Münster, Münster, Germany., Luehrmann V; Institute of Immunology, University of Münster, Münster, Germany., Robeck S; Institute of Immunology, University of Münster, Münster, Germany., Russo A; Institute of Immunology, University of Münster, Münster, Germany., Fischer-Riepe L; Institute of Immunology, University of Münster, Münster, Germany., van den Bosch M; Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., van Lent P; Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Loser K; Department of Human Medicine, University of Oldenburg, Oldenburg, Germany., Gabrilovich DI; AstraZeneca Oncology R&D, Gaithersburg, MD 20878, USA., Hermann S; European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany., Roth J; Institute of Immunology, University of Münster, Münster, Germany; Interdisciplinary Center of Clinical Research (IZKF), University of Münster, Münster, Germany., Vogl T; Institute of Immunology, University of Münster, Münster, Germany; Interdisciplinary Center of Clinical Research (IZKF), University of Münster, Münster, Germany. Electronic address: vogl@uni-muenster.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Aug 29; Vol. 42 (8), pp. 113006. Date of Electronic Publication: 2023 Aug 22.
DOI:	10.1016/j.celrep.2023.113006
Abstrakt:	Immune-suppressive effects of myeloid-derived suppressor cells (MDSCs) are well characterized during anti-tumor immunity. The complex mechanisms promoting MDSC development and their regulatory effects during autoimmune diseases are less understood. We demonstrate that the endogenous alarmin S100A8/A9 reprograms myeloid cells to a T cell suppressing phenotype during autoimmune arthritis. Treatment of myeloid precursors with S100-alarmins during differentiation induces MDSCs in a Toll-like receptor 4-dependent manner. Consequently, knockout of S100A8/A9 aggravates disease activity in collagen-induced arthritis due to a deficit of MDSCs in local lymph nodes, which could be corrected by adoptive transfer of S100-induced MDSCs. Blockade of MDSC function in vivo aggravates disease severity in arthritis. Therapeutic application of S100A8 induces MDSCs in vivo and suppresses the inflammatory phenotype of S100A9ko mice. Accordingly, the interplay of T cell-mediated autoimmunity with a defective innate immune regulation is crucial for autoimmune arthritis, which should be considered for future innovative therapeutic options. Competing Interests: Declaration of interests Dmitry I. Gabrilovich is an employee and shareholder of AstraZeneca. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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