title: NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.
abstract: Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer.
authors.affiliation: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Enyu
authors.initials: E
authors.lastname: Huang
authors.affiliation: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Jiajing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, 518036, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China; Biotherapy Research Center, Fudan University, Shanghai, 200032, China. Electronic address: yiweichu@fudan.edu.cn.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018925:Chemokines; D014409:Tumor Necrosis Factor-alpha
keywords: Colitis-associated colorectal cancer; Inflammatory bowel disease; Natural killer T cell; Neutrophil