info:eu-repo/semantics/article
MERTK as negative regulator of human T cell activation
Fecha
2015-04Registro en:
Cabezón, Raquel; Carrera Silva, Eugenio Antonio; Flórez Grau, Georgina; Errasti, Andrea Emilse; Calderón Gómez, Elisabeth; et al.; MERTK as negative regulator of human T cell activation; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 97; 4; 4-2015; 751-760
0741-5400
Autor
Cabezón, Raquel
Carrera Silva, Eugenio Antonio
Flórez Grau, Georgina
Errasti, Andrea Emilse
Calderón Gómez, Elisabeth
Lozano, Juan José
España, Carolina
Ricart, Elena
Panés, Julián
Rothlin, Carla
Benítez Ribas, Daniel
Resumen
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, whetherMERTK 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-γ production. 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 naïve 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 withMERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.