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Interleukin-7 promotes lung-resident CD14+ monocytes activity in patients with lung squamous carcinoma
Affiliation:1. Department of Thoracic Surgery, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi Province 710061, China;2. Department of Radiation Oncology, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi Province 710061, China;1. College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea;2. Natural Product Research Center, Jeonbuk Branch, Korea Research Institute of Biosciences and Biotechnology, Ipsingil 181, Jeongeup, Jeollabuk-do 56212, Republic of Korea;3. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Geonjae-ro 177, Naju-si, Jeollanam-do 58245, Republic of Korea;4. Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, 30 Baekhak1-gil, Jeongeup, Jeollabuk-do 56212, Republic of Korea;1. Department of Plastic & Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea;2. Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 03080, Republic of Korea;1. Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China;2. The Second Clinical Medical School of the Wenzhou Medical University, 82, Xueyuanxi road, 325027 Wenzhou, China;3. Department of Anesthesiology, The Second Affiliated Hospital of Wen Zhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China;1. Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China;2. Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, China
Abstract:Interleukin (IL)-7 enhances cytokines secretion by CD14+ monocytes, and induces recruitment of monocytes to endothelium. As an important regulator to different types of immune cells, the role of IL-7 in modulation of CD14+ monocytes is still not fully elucidated. Thus, the aim of current study was to investigate the immunoregulatory activity of IL-7 to peripheral and lung-resident CD14+ monocytes in lung squamous carcinoma patients. Thirty-seven lung squamous carcinoma patients and eighteen healthy individuals were enrolled. CD14+ monocytes and CD4+ T cells were purified from both peripheral bloods and bronchoalveolar lavage fluids (BALF). IL-7 expression in plasma and BALF was measured by ELISA, and CD127 expression in peripheral and lung-resident CD14+ monocytes was investigated by real-time PCR and flow cytometry, respectively. Cellular proliferation, cytokine production, and molecules in IL-7 signaling pathway was assessed in CD14+ monocytes in response to IL-7 stimulation. IL-7-induced CD14+ monocytes activity to CD4+ T cells was also assessed in direct and indirect contact co-culture system. There were no remarkable differences of plasma IL-7 concentration or CD127 level between healthy individuals and lung squamous carcinoma patients. However, IL-7 expression was significantly reduced in BALF from tumor site in squamous carcinoma patients, especially in stage III and IV. IL-7 stimulation not only promoted proliferation, cytokines secretion, and STAT-5 phosphorylation in lung-resident CD14+ monocytes, but also enhanced CD14+ monocytes-induced Th1 and T follicular helper cells activation, which presented as elevated interferon-γ and IL-21 secretion by CD4+ T cells. This process required direct cell-to-cell contact, and was dependent on IL-6 secretion. The current data revealed a potential immunopromotive property of IL-7 to lung-resident CD14+ monocytes in lung squamous carcinoma.
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