| Affiliation: | 1. Division of Cancer Immunity, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China CAS Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;2. Department of Biotechnology, College of Life Science, Nanjing Agricultural University, Nanjing, Jiangsu, China;3. Department of General Surgery, Nanjing Lishui People's Hospital, Nanjing, Jiangsu, China;4. The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China;5. Unit of Human Parasite Molecular and Cell Biology, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;6. Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming, China;7. Department of Breast Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China;8. Division of Cancer Immunity, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China |
| Abstract: | Ectoparasites repress host immune responses while they obtain nutrition from their hosts. Understanding the immunosuppressive mechanisms between ectoparasites and their hosts will provide new strategies to develop potential immunosuppressive drugs against immune disorder diseases. Previously, we have discovered that a small peptide, immunoregulin HA, from the horsefly (Hybomitra atriperoides) may play an immunosuppressive role in rat splenocytes. However, the targeting cells and detailed mechanisms of immunoregulin HA in immunosuppressive reactions are not well defined. Here, we show that immunoregulin HA reduces the secretion of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. Interestingly, we discover that the major cytokines repressed by immunoregulin HA are secreted by macrophages, rather than by T cells. Furthermore, immunoregulin HA inhibits macrophage maturation and phagocytosis. Mechanically, the activations of c-JUN N-terminal kinase and extracellular signal-regulated kinase upon LPS stimulation are decreased by immunoregulin HA. Consistently, immunoregulin HA treatment exhibits an anti-inflammatory activity in a mouse model of adjuvant-induced paw inflammation. Taken together, our data reveal that immunoregulin HA conducts the anti-inflammatory activity by blocking macrophage functions. |
