Functional modulation of regulatory T cells and analyses of the underlying mechanisms
Final Report Abstract
Regulatory T cells (Tregs) present in non-lymphoid tissue (NLT), such as skin, colon or lungs are critical for tissue homeostasis, control of inflammation as well as induction of mucosal repair. Recent single-cell RNA sequencing data identified expression of CD83 as part of a NLT-Treg signature, however its biological significance for this specialized Tregs was not yet fully understood. In our previous investigations, we found that conditional deletion of CD83 (CD83cKO) disrupts stability and differentiation of lymphoid Tregs and exacerbates autoimmune responses. The present study explores for the first time the role of CD83 expression by lung-resident Tregs to understand its importance in barrier tissues. We report that CD83- deficient lung Tregs are less differentiated but more activated, resulting in unrestrained T cell activation. Furthermore, using an allergic asthma model, CD83cKO mice showed an accelerated disease progression, with augmented eosinophilic inflammation, driven by Th2-biased T cell responses. CD83cKO Tregs exhibited an enhanced responsiveness to IL-4, leading to insufficient control of Th2- differentiation from naïve T cells. These findings underscore the pivotal role of CD83 in the NLT-Treg-mediated modulation of inflammation, especially in the context of Th2 responses. Overall, our results highlight CD83 as a key player in maintaining tissue homeostasis and modulating inflammatory responses, suggesting potential therapeutic implications for patients suffering from inflammatory disorders such as asthma. However, to reach this goal further studies are necessary.
Publications
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Tilting the Balance: Therapeutic Prospects of CD83 as a Checkpoint Molecule Controlling Resolution of Inflammation. International Journal of Molecular Sciences, 23(2), 732.
Peckert-Maier, Katrin; Royzman, Dmytro; Langguth, Pia; Marosan, Anita; Strack, Astrid; Sadeghi, Shermeh Atefeh; Steinkasserer, Alexander; Zinser, Elisabeth & Wild, Andreas B.
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CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation. Frontiers in Immunology, 14.
Peckert-Maier, Katrin; Langguth, Pia; Strack, Astrid; Stich, Lena; Mühl-Zürbes, Petra; Kuhnt, Christine; Drassner, Christina; Zinser, Elisabeth; Wrage, Marius; Mattner, Jochen; Steinkasserer, Alexander; Royzman, Dmytro & Wild, Andreas B.
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Soluble CD83 modulates human-monocyte-derived macrophages toward alternative phenotype, function, and metabolism. Frontiers in Immunology, 14.
Peckert-Maier, Katrin; Wild, Andreas B.; Sprißler, Laura; Fuchs, Maximilian; Beck, Philipp; Auger, Jean-Philippe; Sinner, Pia; Strack, Astrid; Mühl-Zürbes, Petra; Ramadan, Ntilek; Kunz, Meik; Krönke, Gerhard; Stich, Lena; Steinkasserer, Alexander & Royzman, Dmytro
