title: Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial Damage.
abstract: 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 (TGFβ1) 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.
authors: 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.
authors: Xinyang
authors: X
authors: Song
authors: 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.
authors: Dai
authors: D
authors: Dai
authors: Shanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200001, China.
authors: Xiao
authors: X
authors: He
authors: 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.
authors: Shu
authors: S
authors: Zhu
authors: 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.
authors: Yikun
authors: Y
authors: Yao
authors: 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.
authors: Hanchao
authors: H
authors: Gao
authors: 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.
authors: Jingjing
authors: J
authors: Wang
authors: 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.
authors: Fangfang
authors: F
authors: Qu
authors: 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.
authors: Ju
authors: J
authors: Qiu
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Honglin
authors: H
authors: Wang
authors: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors: Xiaoxia
authors: X
authors: Li
authors: 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.
authors: Nan
authors: N
authors: Shen
authors: 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.
authors: Youcun
authors: Y
authors: Qian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D057809:HEK293 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020381:Interleukin-17; C515963:Traf3ip2 protein, mouse; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2