Production of extracellular adenosine by CD73+ dendritic cells is crucial for induction of tolerance in contact hypersensitivity reactions

• Verfasst von: Silva-Vilches, Cinthia [VerfasserIn]
• Verfasst von: Ring, Sabine [VerfasserIn]
• Verfasst von: Enk, Alexander [VerfasserIn]
• Verfasst von: Mahnke, Karsten [VerfasserIn]
• Titel: Production of extracellular adenosine by CD73+ dendritic cells is crucial for induction of tolerance in contact hypersensitivity reactions
• Verf.angabe: Cinthia Silva-Vilches, Sabine Ring, Jürgen Schrader, Björn E. Clausen, Hans-Christian Probst, Felix Melchior, Hansjörg Schild, Alexander Enk and Karsten Mahnke
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 11 S.
• Fussnoten: Published online 28 October 2018; corrected proof published online 12 January 2019 ; Gesehen am 04.09.2019
• Titel Quelle: Enthalten in: The journal of investigative dermatology
• Ort Quelle: Amsterdam : Elsevier, 1938
• Jahr Quelle: 2019
• Band/Heft Quelle: 139(2019), 3, Seite 541-551
• ISSN Quelle: 1523-1747
• DOI: doi:10.1016/j.jid.2018.10.016
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1675871574

Abstract

Dendritic cells (DCs) express the ecto-5′-nucleotidase CD73 that generates immunosuppressive adenosine (Ado) by dephosphorylation of extracellular Ado monophosphate and diphosphate. To investigate whether CD73-derived Ado has immune-suppressive activity, 2,4-dinitrothiocyanobenzene (DNTB) was applied to skin of wild-type (WT) or CD73-deficient (CD73-/-) mice, followed by sensitization and challenge with 2,4-dinitrofluorobenzene. In this model, we show the induction of tolerance by DNTB against 2,4-dinitrofluorobenzene only in WT but not in CD73-/- mice. Analysis of skin DCs showed increased expression of CD73 after application of DNTB in WT mice. That was accompanied by elevated concentrations of extracellular Ado in the lymph node. Moreover, T cells expressed markers for anergy, namely EGR2 and NDRG1 in DNTB-treated WT mice and they exhibited impaired proliferation upon ex vivo re-stimulation. Similarly, in vitro we observed that Ado-producing WT DCs, but not CD73-/- DCs, rendered transgenic T cells from OTII mice (OTII T cells) hyporeactive, decreased their T-cell costimulatory signaling, and induced up-regulation of EGR2 and NDRG1. Thus, these data show that expression of CD73 by DCs, which triggers elevated levels of extracellular Ado, is a crucial mechanism for the induction of anergic T cells and tolerance.