PD-L1 expression on tolerogenic APCs is controlled by STAT-3

• Verfasst von: Wölfle, Sabine J. [VerfasserIn]
• Verfasst von: Strebovsky, Julia [VerfasserIn]
• Verfasst von: Bartz, Holger [VerfasserIn]
• Verfasst von: Sähr, Aline [VerfasserIn]
• Verfasst von: Arnold, Caroline [VerfasserIn]
• Verfasst von: Kaiser, Claus [VerfasserIn]
• Verfasst von: Dalpke, Alexander [VerfasserIn]
• Verfasst von: Heeg, Klaus [VerfasserIn]
• Titel: PD-L1 expression on tolerogenic APCs is controlled by STAT-3
• Verf.angabe: Sabine J. Wölfle, Julia Strebovsky, Holger Bartz, Aline Sähr, Caroline Arnold, Claus Kaiser, Alexander H. Dalpke and Klaus Heeg
• Jahr: 2011
• Umfang: 12 S.
• Fussnoten: First published: 08 December 2010 ; Gesehen am 05.12.2022
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2011
• Band/Heft Quelle: 41(2011), 2, Seite 413-424
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/eji.201040979
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: DC
• Sach-SW: PD-L1
• Sach-SW: STAT-3
• Sach-SW: TLR
• Sach-SW: Tolerance
• K10plus-PPN: 1824415664

Abstract

During infection, TLR agonists are released and trigger mature as well as differentiating innate immune cells. Early encounter with TLR agonists (R848; LPS) blocks conventional differentiation of CD14+ monocytes into immature dendritic cells (iDCs) resulting in a deviated phenotype. We and others characterized these APCs (TLR-APC) by a retained expression of CD14 and a lack of CD1a. Here, we show in addition, expression of programmed death ligand-1 (PD-L1). TLR-APCs failed to induce T-cell proliferation and furthermore were able to induce CD25+Foxp3+ T regulatory cells (Tregs). Since PD-L1 is described as a key negative regulator and inducer of tolerance, we further analyzed its regulation. PD-L1 expression was regulated in a MAPK/cytokine/STAT-3-dependent manner: high levels of IL-6 and IL-10 that signal via STAT-3 were produced by TLR-APCs. Blocking of STAT-3 activation prevented PD-L1 expression. Moreover, chromatin immunoprecipitation revealed direct binding of STAT-3 to the PD-L1 promoter. Those findings indicate a pivotal role of STAT-3 in regulating PD-L1 expression. MAPKs were indirectly engaged, as blocking of p38 and p44/42 MAPKs decreased IL-6 and IL-10 thus reducing STAT-3 activation and subsequent PD-L1 expression. Hence, during DC differentiation TLR agonists induce a STAT-3-mediated expression of PD-L1 and favor the development of tolerogenic APCs.