Fas signal promotes the immunosuppressive function of regulatory dendritic cells via the ERK/β-catenin pathway
Authors: Cheng Qian
Yizhi Yu
Yongjian Chen
Huazhang An
Qingqing Wang
Yanmei Han
Xuetao Cao
Yi Bai
Zhenhong Guo
Li Qian
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Catenin; Dendritic Cells; ERK; Fas; Tolerance.
Affiliations: From the National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.

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. 

Retracted: No

PubPeer comments:
null, 
 Text from the correction:  The original Fig. 2A mistakenly showed the plot representing apoptotic DCreg cells in the presence of isotype antibody to also represent apoptotic DCreg cells in the presence of Jo2 antibody.  Here is the original Figure 2A, with the duplication. ![file] , 
 The new publishing platform with Elsevier does not make it obvious that there is a correction for this article. The only way I knew that there was a correction was because I had the PubPeer extension installed. There is only an obscure link at the bottom for a  related article and the correction does not automatically download with the PDF. This is terrible in regards to transparency. , 
 #3, I second that emotion. The  Article History states that:  Publication History Accepted: August 13, 2013 Received in revised form: August 12, 2013 Received: October 5, 2012 There is no mention of the correction. Does Elsevier JBC not consider a correction a part of the article s history? ,