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CD83 expression is essential for Treg cell differentiation and stability
Marina Doebbeler, … , Alexander Steinkasserer, Matthias Lechmann
Marina Doebbeler, … , Alexander Steinkasserer, Matthias Lechmann
Published June 7, 2018
Citation Information: JCI Insight. 2018;3(11):e99712. https://doi.org/10.1172/jci.insight.99712.
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Research Article Immunology

CD83 expression is essential for Treg cell differentiation and stability

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Abstract

Foxp3-positive regulatory T cells (Tregs) are crucial for the maintenance of immune homeostasis and keep immune responses in check. Upon activation, Tregs are transferred into an effector state expressing transcripts essential for their suppressive activity, migration, and survival. However, it is not completely understood how different intrinsic and environmental factors control differentiation. Here, we present for the first time to our knowledge data suggesting that Treg-intrinsic expression of CD83 is essential for Treg differentiation upon activation. Interestingly, mice with Treg-intrinsic CD83 deficiency are characterized by a proinflammatory phenotype. Furthermore, the loss of CD83 expression by Tregs leads to the downregulation of Treg-specific differentiation markers and the induction of an inflammatory profile. In addition, Treg-specific conditional knockout mice showed aggravated autoimmunity and an impaired resolution of inflammation. Altogether, our results show that CD83 expression in Tregs is an essential factor for the development and function of effector Tregs upon activation. Since Tregs play a crucial role in the maintenance of immune tolerance and thus prevention of autoimmune disorders, our findings are also clinically relevant.

Authors

Marina Doebbeler, Christina Koenig, Lena Krzyzak, Christine Seitz, Andreas Wild, Thomas Ulas, Kevin Baßler, Dmitry Kopelyanskiy, Alina Butterhof, Christine Kuhnt, Simon Kreiser, Lena Stich, Elisabeth Zinser, Ilka Knippertz, Stefan Wirtz, Christin Riegel, Petra Hoffmann, Matthias Edinger, Lars Nitschke, Thomas Winkler, Joachim L. Schultze, Alexander Steinkasserer, Matthias Lechmann

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Figure 1

CD83cKO mice show increased effector cell activity.

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CD83cKO mice show increased effector cell activity.
(A) Left: Strategy f...
(A) Left: Strategy for the generation of Treg-specific CD83 conditional KO (cKO) animals. Mating of CD83fl/fl mice with Foxp3YFP-Cre mice leads to depletion of flanked exons and thus to specific deletion of CD83 in Foxp3+ T cells. Right: CD83-specific mRNA analysis of Foxp3+ T cells. (B) FACS analysis of splenic T cells from 8- to 12-week-old mice: Treg cells (CD4+Foxp3+). (C) FACS analysis of splenic T cells from 8- to 12-week-old mice: naive T cells (CD4+CD62L+), effector memory T cells (CD4+CD44+), and effector T cells (CD4+CD25+Foxp3–). (D) FACS analysis of splenic T cells from 50- to 72-week-old mice, staining for naive T cells (CD4+CD62L+), effector memory T cells (CD4+CD44+), and effector T cells (CD4+CD25+Foxp3–). KO, n = 8; WT, n = 12. (E) Detection of autoantibodies: cKO and WT sera of young mice at a 1:50 dilution. (F) Mean pixel intensity of ANA level of young (13–17 weeks; n = 3) and aged mice (12–16 months; WT, n = 14; cKO n = 12). Statistical analysis was performed using a Mann-Whitney U test. *P < 0.05, **P < 0.01. Graphs without asterisks are considered not significant.

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