Up‐regulation of galectin‐9 induces cell migration in human dendritic cells infected with dengue virus |
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| Authors: | Yu‐Lin Hsu Mei‐Yi Wang Ling‐Jun Ho Chuan‐Yueh Huang Jenn‐Haung Lai |
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| Affiliation: | 1. Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan;2. Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan;3. Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan;4. Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao‐Yuan, Taiwan |
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| Abstract: | Galectin‐9 (Gal‐9) exerts immunosuppressive effects by inducing apoptosis in T cells that produce interferon‐γ and interleukin (IL)‐17. However, Gal‐9 can be pro‐inflammatory in lipopolysaccharide‐stimulated monocytes. Using microarray analysis, we observed that Gal‐9 was up‐regulated in human dendritic cells (DCs) after dengue virus (DV) infection. The investigation into the immunomodulatory effects and mechanisms of Gal‐9 in DCs exposed to DV revealed that DV infection specifically increased mRNA and protein levels of Gal‐9 but not those of Gal‐1 or Gal‐3. Blocking p38, but not c‐Jun N‐terminal kinase or extracellular signal‐regulated kinase (ERK), inhibited DV‐induced expression of Gal‐9. Reduction in Gal‐9 by small interference RNA treatment suppressed DV‐stimulated migration of DCs towards the chemoattractants CCL19 and CCL21. In addition, DV‐induced IL‐12p40 production was reduced after knockdown of Gal‐9 in DCs. Furthermore, Gal‐9 deficiency suppressed DV‐induced activation of nuclear factor‐κB. Inhibition of DV‐induced DC migration under conditions of Gal‐9 deficiency was mediated through suppressing ERK activation but not by regulating the expression of CCR7, the receptor for CCL19 and CCL21. Both the reduction in IL‐12 production and the suppression of ERK activity might account for the inhibition of DV‐induced DC migration after knockdown of Gal‐9. In summary, this study reveals the roles of Gal‐9 in DV‐induced migration of DCs. The findings indicate that Gal‐9 might be a therapeutic target for preventing immunopathogenesis induced by DV infection. |
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| Keywords: | dengue virus dendritic cells galectin‐9 cell migration immune response mitogen‐activated protein kinase |
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