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.