PMID- 26320657
OWN - NLM
STAT- MEDLINE
DCOM- 20160104
LR  - 20150917
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Linking)
VI  - 43
IP  - 3
DP  - 2015 Sep 15
TI  - Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial 
      Damage.
PG  - 488-501
LID - S1074-7613(15)00311-8 [pii]
LID - 10.1016/j.immuni.2015.06.024 [doi]
AB  - The intestinal epithelial barrier plays a critical role in the mucosal immunity. 
      However, it remains largely unknown how the epithelial barrier is maintained 
      after damage. Here we show that growth factor FGF2 synergized with interleukin-17 
      (IL-17) to induce genes for repairing of damaged epithelium. FGF2 or IL-17 
      deficiency resulted in impaired epithelial proliferation, increased 
      pro-inflammatory microbiota outgrowth, and consequently worse pathology in a 
      DSS-induced colitis model. The dysregulated microbiota in the model induced 
      transforming growth factor beta 1 (TGFbeta1) expression, which in turn induced FGF2 
      expression mainly in regulatory T cells. Act1, an essential adaptor in IL-17 
      signaling, suppressed FGF2-induced ERK activation through binding to adaptor 
      molecule GRB2 to interfere with its association with guanine nucleotide exchange 
      factor SOS1. Act1 preferentially bound to IL-17 receptor complex, releasing its 
      suppressive effect on FGF2 signaling. Thus, microbiota-driven FGF2 and IL-17 
      cooperate to repair the damaged intestinal epithelium through Act1-mediated 
      direct signaling cross-talk.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Song, Xinyang
AU  - Song X
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Dai, Dai
AU  - Dai D
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - He, Xiao
AU  - He X
AD  - Shanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai 200001, China.
FAU - Zhu, Shu
AU  - Zhu S
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Yao, Yikun
AU  - Yao Y
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Gao, Hanchao
AU  - Gao H
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Wang, Jingjing
AU  - Wang J
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Qu, Fangfang
AU  - Qu F
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Qiu, Ju
AU  - Qiu J
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China.
FAU - Wang, Honglin
AU  - Wang H
AD  - Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200025, China.
FAU - Li, Xiaoxia
AU  - Li X
AD  - Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, 
      Cleveland, OH 44195, USA.
FAU - Shen, Nan
AU  - Shen N
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China; Shanghai Institute of 
      Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200001, China; State Key Laboratory of Oncogenes and Related 
      Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200032, China; Center for Autoimmune Genomics and 
      Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 
      45229, USA. Electronic address: nanshensibs@gmail.com.
FAU - Qian, Youcun
AU  - Qian Y
AD  - The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao 
      Tong University School of Medicine, Shanghai 200031, China; Shanghai Institute of 
      Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200001, China. Electronic address: ycqian@sibs.ac.cn.
LA  - eng
SI  - GEO/GSE70993
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150825
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Interleukin-17)
RN  - 0 (Traf3ip2 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/immunology/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Colitis/genetics/immunology/metabolism
MH  - Fibroblast Growth Factor 2/genetics/*immunology/metabolism
MH  - Gene Expression Profiling/methods
MH  - HEK293 Cells
MH  - HT29 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Interleukin-17/genetics/*immunology/metabolism
MH  - Intestinal Mucosa/immunology/microbiology/pathology
MH  - Intestines/*immunology/microbiology/pathology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microbiota/genetics/immunology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
MH  - Transforming Growth Factor beta/genetics/immunology/metabolism
MH  - Wound Healing/immunology
EDAT- 2015/09/01 06:00
MHDA- 2016/01/05 06:00
CRDT- 2015/09/01 06:00
PHST- 2014/09/08 00:00 [received]
PHST- 2015/04/27 00:00 [revised]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/09/01 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/01/05 06:00 [medline]
AID - S1074-7613(15)00311-8 [pii]
AID - 10.1016/j.immuni.2015.06.024 [doi]
PST - ppublish
SO  - Immunity. 2015 Sep 15;43(3):488-501. doi: 10.1016/j.immuni.2015.06.024. Epub 2015 
      Aug 25.