Author:
Schuette Verena,Embgenbroich Maria,Ulas Thomas,Welz Meike,Schulte-Schrepping Jonas,Draffehn Astrid M.,Quast Thomas,Koch Katharina,Nehring Melanie,König Jessica,Zweynert Annegret,Harms Frederike L.,Steiner Nancy,Limmer Andreas,Förster Irmgard,Berberich-Siebelt Friederike,Knolle Percy A.,Wohlleber Dirk,Kolanus Waldemar,Beyer Marc,Schultze Joachim L.,Burgdorf Sven
Abstract
The mannose receptor (MR) is an endocytic receptor involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8+ T-cell activity. We demonstrate that MR expression on dendritic cells (DCs) impaired T-cell cytotoxicity in vitro and in vivo. This regulatory effect of the MR was mediated by a direct interaction with CD45 on the T cell, inhibiting its phosphatase activity, which resulted in up-regulation of cytotoxic T-lymphocyte–associated Protein 4 (CTLA-4) and the induction of T-cell tolerance. Inhibition of CD45 prevented expression of B-cell lymphoma 6 (Bcl-6), a transcriptional inhibitor that directly bound the CTLA-4 promoter and regulated its activity. These data demonstrate that endocytic receptors expressed on DCs contribute to the regulation of T-cell functionality.
Publisher
Proceedings of the National Academy of Sciences
Cited by
58 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献