title: PTEN in smooth muscle cells is essential for colonic immune homeostasis.
abstract: Colonic immune homeostasis is essential for normal gastrointestinal tract functioning. In this study, we report that specific gene targeting of phosphatase and tensin homolog (PTEN) in smooth muscle cells caused age-related colonic lymphoid hyperplasia followed by global immune activation in mice. Beginning at 5 weeks of age, these mutant mice displayed massive neutrophil infiltration in the colonic lamina propria. The gene expression levels of pro-inflammatory cytokines and chemokines, including those code for monocyte chemotactic protein-1 (Mcp-1), stromal cell-derived factor 1α (Sdf-1α), and chemokine (C-C motif) ligand 28 (Ccl-28), were upregulated in the colon. Accordingly, permeability and proliferation of the colonic epithelium was compromised. These abnormalities were alleviated to a great extent when the mutants were crossed with Akt1-null mice, indicating that the pathogenesis was mediated by Akt1 signaling. Our results suggest that in smooth muscle cells, PTEN is crucial for maintaining colonic immune homeostasis.
authors.affiliation: Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Nanjing 210061, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.affiliation: Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China.
authors.forename: Jingyue
authors.initials: J
authors.lastname: Xu
authors.affiliation: Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Gu
authors.affiliation: Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Nanjing 210061, China. Electronic address: gaoxiang@nju.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D019310:Pseudolymphoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Akt1; Immune activation; Lymphoid follicle; PTEN; Smooth muscle cell