title: Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis.
abstract: In response to changes in microenvironment, macrophages polarize into functionally distinct phenotypes, playing a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the effects of sorting nexin 10 (SNX10), a protein involved in endosomal trafficking and osteoclast maturation, on regulation of macrophage polarization and progression of mouse colitis. Our results revealed that SNX10 deficiency increased the population of M2-type monocytes/macrophages, and protected against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). By in vitro study, we showed that deficiency of SNX10 polarized macrophages derived from mouse bone marrow or human peripheral blood mononuclear cells (PBMCs) towards an anti-inflammatory M2 phenotype, which partially reversed by SNX10 plasmid transfection. Adoptive transfer of SNX10(-/-) macrophages ameliorated colitis in WT mice. However, transfer of WT macrophages exacerbated colitis in SNX10(-/-) mice. Our data disclose a crucial role and novel function for SNX10 in macrophage polarization. Loss of SNX10 function may be a potential promising therapeutic strategy for IBD.
authors: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors: Yan
authors: Y
authors: You
authors: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Chun
authors: C
authors: Zhou
authors: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Dong
authors: D
authors: Li
authors: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors: Zhong-Lian
authors: ZL
authors: Cao
authors: The Translational Medicine Research Center, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
authors: Weixing
authors: W
authors: Shen
authors: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Wan-Zhen
authors: WZ
authors: Li
authors: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors: Sulin
authors: S
authors: Zhang
authors: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors: Bin
authors: B
authors: Hu
authors: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.|Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Xiaoyan
authors: X
authors: Shen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology*; D003106:Colon / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D051379:Mice; D018345:Mice, Knockout; D058305:Sorting Nexins / Q000235:genetics / Q000276:immunology*
chemical_list: D058305:Sorting Nexins; D016264:Dextran Sulfate