1. MERTK as negative regulator of human T cell activation
- Author
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Cabezo´n, Raquel, Carrera‐Silva, E. Antonio, Flo´rez‐Grau, Georgina, Errasti, Andrea E., Caldero´n‐Go´mez, Elisabeth, Lozano, Juan Jose´, a, Ricart, Elena, Pane´s, Julia´n, Rothlin, Carla Vanina, Beni´tez‐Ribas, Daniel, and a
- Abstract
MERTK on DCs is a potent suppressor of human T cell activation through competition for PROS1 interaction in T cells. The aim of this study was to test the hypothesis whether MERTK, which is up‐regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whether MERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex‐induced human tol‐DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN‐γproduction. Additionally, we identify a previously unrecognized noncell‐autonomous regulatory function of MERTK expressed on DCs. Mer‐Fc protein, used to mimic MERTK on DCs, suppresses nai¨ve and antigen‐specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction with MERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.
- Published
- 2015
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