| First Author | Peckert-Maier K | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1085742 | PubMed ID | 36875129 |
| Mgi Jnum | J:335138 | Mgi Id | MGI:7443383 |
| Doi | 10.3389/fimmu.2023.1085742 | Citation | Peckert-Maier K, et al. (2023) CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation. Front Immunol 14:1085742 |
| abstractText | Excessive macrophage (Mphi) activation results in chronic inflammatory responses or autoimmune diseases. Therefore, identification of novel immune checkpoints on Mphi, 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 Mphi (AAM). Using a conditional KO mouse (cKO), we show that CD83 is important for the phenotype and function of pro-resolving Mphi. CD83-deletion in IL-4 stimulated Mphi results in decreased levels of inhibitory receptors, such as CD200R and MSR-1, which correlates with a reduced phagocytic capacity. In addition, CD83-deficient Mphi 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 Mphi reveal an increased production of pro-inflammatory mediators, such as TNF-alpha, IL-6, CXCL1 and G-CSF. Furthermore, we show that CD83-deficient Mphi 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 Mphi 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 Mphi 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 Mphi. |
