Associate Scientist Hills Pet Nutrition Topeka, Kansas, United States
Abstract:
Background: Pathogenesis of inflammatory bowel disease (IBD) is multifactorial. Intestinal inflammation due to increased pro-inflammatory cytokines and chemokines leads to mucosal barrier dysfunction and subsequent aberrant immune response.
Hypothesis: Tissue-resident immune cells including excessive activation of T lymphocytes contributes to the pathogenesis of IBD.
Animals: Dogs, from Hill’s colony, were diagnosed with IBD clinically by a veterinarian via endoscopy and re-confirmed via pathology at necropsy at end of their natural life (n=12; 5.3-15.3yr). Control dogs exhibited no signs of IBD during life (n=12, 6.0-15.0yr)
Methods: We assessed gene expression, in a retrospective study, in transverse colon tissue collected at necropsy. RNA was extracted from tissues and gene expression investigated using Canine Immuno-Oncology panel of the NanoString nCounter® platform. Analysis performed using nSolver software.
Results: Significant increase in 24 genes in IBD compared to controls. Markers of CD8+ T cells were upregulated in IBD with CD8B increased 1.55 fold (p< 0.05). CD8 antigen is a cell surface glycoprotein found on most cytotoxic T cells. KLRG1 (2.01 fold, p< 0.05), receptor for E-cadherin and expressed on CD8+ T-cells; Granzyme B (1.86, p< 0.05), a protease secreted by CD8+ T cells and natural killer cells, and FLT3 (1.47, p< 0.05), a receptor expressed on CD103+ dendritic cells which can mediate CD8+ T cell proliferation and activation, were increased in IBD.
Conclusions: Upregulation of CD8+ T cells and KLRG1 is consistent with ulcerative colitis in humans. Results indicate an important role of CD8+ lymphocytes in IBD and diverse immune targets for reducing inflammation in canines with IBD.
