Soluble CD83 modulates human-monocyte-derived macrophages toward alternative phenotype, function, and metabolism.

Peckert-Maier K, Wild A, Sprißler L, Fuchs M, Beck P, Auger JP, Sinner P, Strack A, Mühl-Zürbes P, Ramadan N, Kunz M, Krönke G, Stich L, Steinkasserer A, Royzman D (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 14

DOI: 10.3389/fimmu.2023.1293828

Abstract

Alterations in macrophage (Mφ) polarization, function, and metabolic signature can foster development of chronic diseases, such as autoimmunity or fibrotic tissue remodeling. Thus, identification of novel therapeutic agents that modulate human Mφ biology is crucial for treatment of such conditions. Herein, we demonstrate that the soluble CD83 (sCD83) protein induces pro-resolving features in human monocyte-derived Mφ biology. We show that sCD83 strikingly increases the expression of inhibitory molecules including ILT-2 (immunoglobulin-like transcript 2), ILT-4, ILT-5, and CD163, whereas activation markers, such as MHC-II and MSR-1, were significantly downregulated. This goes along with a decreased capacity to stimulate alloreactive T cells in mixed lymphocyte reaction (MLR) assays. Bulk RNA sequencing and pathway analyses revealed that sCD83 downregulates pathways associated with pro-inflammatory, classically activated Mφ (CAM) differentiation including HIF-1A, IL-6, and cytokine storm, whereas pathways related to alternative Mφ activation and liver X receptor were significantly induced. By using the LXR pathway antagonist GSK2033, we show that transcription of specific genes (e.g., PPARG, ABCA1, ABCG1, CD36) induced by sCD83 is dependent on LXR activation. In summary, we herein reveal for the first time mechanistic insights into the modulation of human Mφ biology by sCD83, which is a further crucial preclinical study for the establishment of sCD83 as a new therapeutical agent to treat inflammatory conditions.

Authors with CRIS profile

Laura Sprißler Institute of Clinical and Molecular Virology Philipp Beck Department of Immune Modulation Jean-Philippe Auger Department of Medicine 3 – Rheumatology and Immunology Astrid Strack Department of Immune Modulation Meik Kunz
Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Alexander Steinkasserer Professur für Experimentelle Dermatologie Dmytro Royzman Department of Immune Modulation

Involved external institutions

Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM) / Fraunhofer Institute for Toxicology and Experimental Medicine DE Germany (DE)

How to cite

APA:

Peckert-Maier, K., Wild, A., Sprißler, L., Fuchs, M., Beck, P., Auger, J.-P.,... Royzman, D. (2023). Soluble CD83 modulates human-monocyte-derived macrophages toward alternative phenotype, function, and metabolism. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1293828

MLA:

Peckert-Maier, Katrin, et al. "Soluble CD83 modulates human-monocyte-derived macrophages toward alternative phenotype, function, and metabolism." Frontiers in Immunology 14 (2023).

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