Cyclic AMP-Responsive Element-Binding Protein (CREB) is Critical in Autoimmunity by Promoting Th17 but Inhibiting Treg Cell Differentiation
Authors: Dehui Chang
Chen Dong
Lu Ni
Huiping Lu
Yu Jiang
Aibo Wang
Xiaohu Wang
Bo Zhong
Byung-Seok Kim
Xindong Liu
Xuexian Yang
Journal: EBioMedicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Autoimmune diseases; CREB; Th17 cells; Treg cells.
Affiliations: Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: ., Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China., Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030, USA., Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China., School of Life Sciences, Wuhan University, Wuhan 430072, China., Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, USA.

Abstract:  The molecular mechanisms that govern differential T cell development into pro-inflammatory Th17 vs. regulatory T (Treg) cells remain unclear. Here, we show that selective deletion of CREB in T cells or Th17 cells impaired Th17 cell differentiation in vitro and in vivo, and led to resistance to autoimmune diseases. Mechanistically, CREB, activated by CD3-PKC-œ¥ signaling, plays a key role in regulating Th17 cell differentiation, at least in part through directly binding to the Il17-Il17f gene locus. Unexpectedly, although dispensable for FOXP3 expression and for the homeostasis and suppressive function of thymus-derived Treg cells, CREB negatively regulates the survival of TGF-Œ≤-induced Treg cells, and deletion of CREB resulted in increased FOXP3+ Treg cells in the intestine and protection in a colitis model. Thus, CREB is critical in autoimmune diseases by promoting Th17 cell and inhibiting de novo Treg cell generation. 

Retracted: No

PubPeer comments:
 Figure 4 appears to have a repeated image. Apologies if Iu2019ve misunderstood. ***  *** Figure with legend  , 
 I will contact will the first author and check the raw data of this figure. Thank you very much for pointing this issue for us! , 
 Dear Actinopolyspora Biskrensisuff0c Thank you very much for raising this concern. Indeed, the image of Figure 4A (left panel; Scramble) duplicated the image of Figure 4C (left panel; Control siRNA). It turned out to be an honest mistake made by the first author when she assembled different panels of Figure 4 (the duplicated two panels are close to each other). She did not manipulate the data in any way. The corresponding authors have checked all the original data and analyses to prove her innocence. We have contacted the journal explaining what has happened and sent a new version of Figure 4 to address this issue. The corrected figure does not affect the interpretation or conclusions of this paper. We apologize to our readers for any confusion this unintentional error might have caused. , 
 Returning to Figure 4, I have identified additional potential overlaps (cyan and yellow boxes). As the authors do not appear to have successfully contacted the journal, I will attempt to do so now. ***  ,