CD83 expression is essential for Treg cell differentiation and stability

Döbbeler M, Koenig C, Krzyzak L, Seitz C, Wild A, Ulas T, Bassler K, Kopelyanskiy D, Butterhof A, Kuhnt C, Kreiser S, Stich L, Zinser E, Knippertz I, Wirtz S, Riegel C, Hoffmann P, Edinger M, Nitschke L, Winkler T, Schultze JL, Steinkasserer A, Lechmann M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

JCI Insight American Society for Clinical Investigation

Book Volume: 3

Journal Issue: 11

DOI: 10.1172/jci.insight.99712

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 with CRIS profile

Marina Döbbeler Department of Immune Modulation Lena Krzyzak Professur für Experimentelle Dermatologie Andreas Wild Lehrstuhl für Biochemie und Molekulare Medizin Simon Kreiser Professur für Experimentelle Dermatologie Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Lars Nitschke Professur für Genetik Thomas Winkler Professur für Genetik Alexander Steinkasserer Professur für Experimentelle Dermatologie Matthias Lechmann Department of Immune Modulation

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Döbbeler, M., Koenig, C., Krzyzak, L., Seitz, C., Wild, A., Ulas, T.,... Lechmann, M. (2018). CD83 expression is essential for Treg cell differentiation and stability. JCI Insight, 3(11). https://dx.doi.org/10.1172/jci.insight.99712

MLA:

Döbbeler, Marina, et al. "CD83 expression is essential for Treg cell differentiation and stability." JCI Insight 3.11 (2018).

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