Immunohistochemical investigation of Foxp3 expression in the intestine in healthy and diseased dogs

Johannes Junginger,Ingo Nolte,Marion Hewicker-Trautwein,Ulrike Schwittlick,Frederik Lemensieck

doi:10.1186/1297-9716-43-23

Abstract

Intestinal immune regulation including development of oral tolerance is of great importance for the maintenance of intestinal homeostasis. Concerning this, regulatory T cells (Tregs) occupy a pivotal role in cell-mediated immunosuppression. Dysregulation of mucosal immunology leading to an abnormal interaction with commensal bacteria is suggested to play a key role in the pathogenesis of Inflammatory Bowel Disease (IBD) in men and dogs. The aim of this study was to characterise the expression of Foxp3 in the normal canine gut of 18 dogs (mean age: 6.03 years), in 16 dogs suffering from IBD (mean age: 5.05 years), and of 6 dogs with intestinal nematode infection (mean age: 0.87 years) using immunohistochemistry. In the duodenum, Tregs in healthy dogs declined from villi (median: 10.67/62 500 μm2) to crypts (median: 1.89/62 500 μm2). Tregs were further increased in the villi of middle-aged dogs (median: 18.92/62 500 μm2) in contrast to juvenile (median: 3.50/62 500 μm2) and old (median: 9.56/62 500 μm2) individuals. Compared to healthy controls, animals suffering from IBD revealed reduced numbers of Tregs in duodenal villi (median: 4.13/62 500 μm2). Dogs with intestinal nematode infection displayed increased numbers of Tregs (median: 21.06/62 500 μm2) compared to healthy animals.Age-related changes indicate a progressive establishment of oral tolerance and immunosenescence in the canine elderly. The results further suggest that a defect in Treg homeostasis may be involved in the pathogenesis of canine IBD. In contrast, increased numbers of Tregs in the duodenum may be due to nematode infection.

Highlights

The vertebrate’s gut is perpetually exposed to an enormous amount of different microorganisms and food proteins with antigenic properties that are essential for the individual’s life
T helper cells with regulatory properties (Tregs) are characterised by the expression of CD4, CD25 [7], and the highly conserved transcription factor Forkhead box P3 (Foxp3) [14] serving a pivotal role in stabilising their regulatory properties [15]
Histopathological findings In dogs lacking clinical and pathomorphological signs of gastrointestinal diseases, mild histopathological findings were present in the gut

Summary

Introduction

The vertebrate’s gut is perpetually exposed to an enormous amount of different microorganisms and food proteins with antigenic properties that are essential for the individual’s life. Immune regulation can be either mediated by regulatory cytokines (e.g. tissue growth factor (TGF)-b, interleukin (IL)-10) or cellular interactions Today, it is well-known that specialised T helper cells with regulatory properties (Tregs) play an important part in immune regulation [5,6]. Oral tolerance is supposed to be mainly mediated by the induction and expansion of Tregs in the context of specialised tolerogenic dendritic cells in the gut [11,12,13] Alongside their regulatory capacity, Tregs are characterised by the expression of CD4, CD25 [7], and the highly conserved transcription factor Forkhead box P3 (Foxp3) [14] serving a pivotal role in stabilising their regulatory properties [15]

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