title: CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response.
abstract: Accumulating evidence suggests that chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) may contribute to the pathogenesis of allergic asthma. However, the underlying molecular mechanisms remain to be fully understood. T-helper 17 cells (Th17) and T-cytotoxic 17 cells (Tc17) have been implicated in the development of several allergic disorders, including asthma. The present study aimed to explore the association between CXCL12 signaling and Th17/Tc17 cells in the development of asthma. Ovalbumin (OVA)-sensitized BALB/c mice were treated with AMD3100, a specific CXCR4 antagonist, prior to OVA challenge. Following the final allergen (OVA) challenge, airway responsiveness to methacholine, influx of inflammatory cells to the airway, and cytokine levels in the bronchoalveolar lavage fluids (BALF) and lung homogenate were assessed. Interleukin (IL)-17-expressing CD3+CD8-lymphocytes (Th17 cells) and IL-17+CD3+CD8+lymphocytes (Tc17 cells) isolated from lung tissue samples were detected by flow cytometry. The results of the present study demonstrated that administration of AMD3100 significantly decreased airway responsiveness to methacholine, attenuated the influx of inflammatory cells to the airway and reduced the levels of IL-4, IL-5 and IL-13 in the BALF. Furthermore, AMD3100 significantly reduced the increased number of lung Th17 and Tc17 cells as well as the levels of IL-17 in the lung homogenate induced by OVA challenge. In conclusion, the CXCR4 inhibitor suppresses the asthmatic response, which is associated with attenuation of the Th17 and Tc17 cell immune response.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Huilong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xiangqin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jieming
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Hansvin
authors.initials: H
authors.lastname: Bunjhoo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jungang
authors.initials: J
authors.lastname: Xie
authors.affiliation: Center for Biomedical Research, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Congyi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Weining
authors.initials: W
authors.lastname: Xiong
keywords: C-X-C chemokine receptor type 4; T-cytotoxic 17 cells; T-helper 17 cells; asthma