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J Biol Chem. 2013 Sep 27;288(39):27825-35. doi: 10.1074/jbc.M112.425751. Epub 2013 Aug 13.

Fas signal promotes the immunosuppressive function of regulatory dendritic cells via the ERK/β-catenin pathway.

Author information

1
From the National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.

Erratum in

  • J Biol Chem. 2014 Feb 28;289(9):5534-5.

Abstract

Dendritic cells (DCs) play important roles in the initiation of immune response and also in the maintenance of immune tolerance. Now, many kinds of regulatory DCs with different phenotypes have been identified to suppress immune response and contribute to the control of autoimmune diseases. However, the mechanisms by which regulatory DCs can be regulated to exert the immunosuppressive function in the immune microenvironment remain to be fully investigated. In addition, how T cells, once activated, can feedback affect the function of regulatory DCs during immune response needs to be further identified. We previously identified a unique subset of CD11b(hi)Ia(low) regulatory DCs, differentiated from mature DCs or hematopoietic stem cells under a stromal microenvironment in spleen and liver, which can negatively regulate immune response in a feedback way. Here, we show that CD11b(hi)Ia(low) regulatory DCs expressed high level of Fas, and endothelial stromal cell-derived TGF-β could induce high expression of Fas on regulatory DCs via ERK activation. Fas ligation could promote regulatory DCs to inhibit CD4(+) T cell proliferation more significantly. Furthermore, Fas ligation preferentially induced regulatory DCs to produce IL-10 and IP-10 via ERK-mediated inactivation of GSK-3 and subsequent up-regulation of β-catenin. Interestingly, activated T cells could promote regulatory DCs to secrete more IL-10 and IP-10 partially through FasL. Therefore, our results demonstrate that Fas signal, at least from the activated T cells, can promote the immunosuppressive function of Fas-expressing regulatory DCs, providing a new manner for the regulatory DCs to regulate adaptive immunity.

KEYWORDS:

Catenin; Dendritic Cells; ERK; Fas; Tolerance

PMID:
23943615
PMCID:
PMC3784698
DOI:
10.1074/jbc.M112.425751
[Indexed for MEDLINE]
Free PMC Article

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