Preliminary Study of CCR9 and MAdCAM-1 Upregulation and Immune Imbalance in Canine Chronic Enteropathy: Findings Based on Histopathological Analysis

Abstract

Canine chronic enteropathy (CE) is a gastrointestinal disorder characterized by persistent or recurrent digestive symptoms lasting more than three weeks. It shares similarities with human inflammatory bowel disease but its immunopathogenesis remains poorly characterized in dogs. The aim of this study was to characterize the local and systemic immune profile of dogs with CE by assessing cytokine and chemokine expression in serum and intestinal tissue, as well as the mRNA expression of immune-related receptors such as integrins, chemokine receptors, and cytokines. Duodenal biopsies and blood samples were collected from five dogs diagnosed with a CE and five healthy controls. Serum concentrations of cytokines and chemokines were determined by multiplex ELISA, and mRNA expression in the intestinal mucosa was analyzed by quantitative PCR. Dogs with a CE showed increased expression of pro-inflammatory cytokines, including TNF-α and IFN-γ, and increased concentrations of chemokines such as CXCL10 and CCL2 in both serum and tissue samples. Increased mRNA expression of the chemokine receptor CCR9 and the adhesion molecule MAdCAM-1 were also observed in intestinal samples. These findings provide new insights into the immune response involved in CE and may aid the development of future diagnostic biomarkers and targeted therapies for canine chronic enteropathies.

Keywords: CCR9; MAdCAM-1; canine; chemokines; chronic inflammatory enteritis; cytokines; immune profile.

Figure A1

Macroscopic and microscopic evaluation of the duodenum in dogs. (A) Representative duodenal image from a dog with chronic enteropathy (CE), showing macroscopic lesions associated with inflammation. (B) Duodenum from a healthy control animal, showing mildly irregular mucosa and subtle discoloration. (C) Duodenal biopsy from a CE dog, exhibiting lymphoplasmacytic infiltrate (asterisk) and stromal fibrosis (arrow) in the lamina propria. (D) Duodenal biopsy from a healthy dog, with no histological abnormalities. All dogs in the CE group were diagnosed with lymphoplasmacytic enteritis based on histopathological analysis.

Figure 1

Serum cytokine concentrations in healthy control dogs (n = 5) and dogs with chronic enteropathy (CE; n = 5). The graphs show the concentrations of (a) interferon-γ (IFN-γ), (b) tumor necrosis factor-α (TNF-α), and (c) interleukin-18 (IL-18). Data are presented as single values with a median. Asterisks (**) indicate statistically significant differences (p < 0.05); ns = not significant.

Figure 2

Serum chemokine concentrations in healthy control dogs (n = 5) and dogs with chronic enteropathy (CE; n = 5). The graphs show the concentrations of (a) IL-8 (CXCL8), (b) CXCL10, and (c) CCL2. Data are presented as single values with a median. Asterisks (*) indicate statistically significant differences (p < 0.05); ns = not significant.

Figure 3

Relative mRNA expression in the duodenal mucosa of healthy control dogs (n = 5) and dogs with chronic enteropathy (CE; n = 5). The graphs show the expression of (a) interferon-γ (IFN-γ), (b) interleukin-4 (IL-4), (c) interleukin-17 (IL-17), (d) CCL25, and (e) CXCL8 (IL-8). Data are presented as single values with a median. Asterisks (*) indicate statistically significant differences (** p < 0.01; *** p < 0.001; **** p < 0.0001; ns = not significant (p ≥ 0.05)).

Figure 4

Relative mRNA expression of transcription factors in the duodenal mucosa of healthy control dogs (n = 5) and dogs with chronic enteropathy (CE; n = 5). The graphs show expression of (a) T-bet, (b) GATA3, and (c) Foxp3. Data are presented as single values with a median. Asterisks (***) indicate statistically significant differences (p < 0.05); ns = not significant.

Figure 5

Relative mRNA expression of adhesion and chemokine receptors in the duodenal mucosa of healthy control dogs (n = 5) and dogs with chronic enteropathy (CE; n = 5). The graphs show expression of (a) MAdCAM-1, (b) CCR2, (c) CCR9, and (d) CCR3. Data are presented as single values with a median. Asterisks (*) indicate statistically significant differences (** p < 0.01; **** p < 0.0001).