Proc Natl Acad Sci U S A. 2016 Sep 20.

Mannose receptor induces T-cell tolerance via inhibition of CD45 and up-regulation of CTLA-4.

Schuette V, Embgenbroich M, Ulas T, Welz M, Schulte-Schrepping J, Draffehn AM, Quast T, Koch K, Nehring M, König J, Zweynert A, Harms FL, Steiner N, Limmer A, Förster I, Berberich-Siebelt F, Knolle PA, Wohlleber D, Kolanus W, Beyer M, Schultze JL, Burgdorf S

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.

PMID: 27601670 [PubMed - in process]