期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 97, 期 4, 页码 751-760出版社
WILEY
DOI: 10.1189/jlb.3A0714-334R
关键词
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资金
- Ministerio de Ciencia e Innovacion [SAF 2009-07272]
- Ministerio de Sanidad y Politica Social [TRA-097]
- Instituto Carlos III [FIS PI13/01585]
- U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases [R01 AI089824]
- Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd)
- Instituto de Salud Carlos III
- Generalitat de Catalunya
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-gamma 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 naive 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.
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