Peckert-Maier K, Langguth P, Strack A, Stich L, Mühl-Zürbes P, Kuhnt C, Drassner C, Zinser E, Wrage M, Mattner J, Steinkasserer A, Royzman D, Wild A (2023)
Publication Type: Journal article
Publication year: 2023
Book Volume: 14
DOI: 10.3389/fimmu.2023.1085742
Excessive macrophage (M phi) activation results in chronic inflammatory responses or autoimmune diseases. Therefore, identification of novel immune checkpoints on M phi, which contribute to resolution of inflammation, is crucial for the development of new therapeutic agents. Herein, we identify CD83 as a marker for IL-4 stimulated pro-resolving alternatively activated M phi (AAM). Using a conditional KO mouse (cKO), we show that CD83 is important for the phenotype and function of pro-resolving M phi. CD83-deletion in IL-4 stimulated M phi results in decreased levels of inhibitory receptors, such as CD200R and MSR-1, which correlates with a reduced phagocytic capacity. In addition, CD83-deficient M phi upon IL-4 stimulation, show an altered STAT-6 phosphorylation pattern, which is characterized by reduced pSTAT-6 levels and expression of the target gene Gata3. Concomitantly, functional studies in IL-4 stimulated CD83 KO M phi reveal an increased production of pro-inflammatory mediators, such as TNF-alpha, IL-6, CXCL1 and G-CSF. Furthermore, we show that CD83-deficient M phi have enhanced capacities to stimulate the proliferation of allo-reactive T cells, which was accompanied by reduced frequencies of Tregs. In addition, we show that CD83 expressed by M phi is important to limit the inflammatory phase using a full-thickness excision wound healing model, since inflammatory transcripts (e.g. Cxcl1, Il6) were increased, whilst resolving transcripts (e.g. Ym1, Cd200r, Msr-1) were decreased in wounds at day 3 after wound infliction, which reflects the CD83 resolving function on M phi also in vivo. Consequently, this enhanced inflammatory milieu led to an altered tissue reconstitution after wound infliction. Thus, our data provide evidence that CD83 acts as a gatekeeper for the phenotype and function of pro-resolving M phi.
APA:
Peckert-Maier, K., Langguth, P., Strack, A., Stich, L., Mühl-Zürbes, P., Kuhnt, C.,... Wild, A. (2023). CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1085742
MLA:
Peckert-Maier, Katrin, et al. "CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation." Frontiers in Immunology 14 (2023).
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