MERTK as negative regulator of human T cell activation.

Abstract:

: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-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 with MERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.

journal_name

J Leukoc Biol

authors

Cabezón R,Carrera-Silva EA,Flórez-Grau G,Errasti AE,Calderón-Gómez E,Lozano JJ,España C,Ricart E,Panés J,Rothlin CV,Benítez-Ribas D

doi

10.1189/jlb.3A0714-334R

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

751-60

issue

4

eissn

0741-5400

issn

1938-3673

pii

jlb.3A0714-334R

journal_volume

97

pub_type

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