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

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.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. Concerning this high antigenic load, a complex immunological network has been developed representing an effective protection composed of more structured areas (lymphoid aggregates, Peyer's patches, lymphoglandular complexes, and mesenteric lymph nodes) as well as diffuse parts (lamina propria leucocytes and intraepithelial lymphocytes) [1-4]. Due to the intestinal colocalisation of commensal bacteria and pathogens, mechanisms preventing specific immune responses against orally administrated antigens (e.g. food proteins and commensal bacteria) termed as oral tolerance are as much as essential as the induction of specific immune responses against pathogenic organisms.In general, immune regulation can be either mediated by regulatory cytokines (e.g. tissue growth factor (TGF)-β, 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]. Depletion of these cells or mutations of related transcription factors provokes severe cases of autoimmune diseases and chronic inflammatory disorders as described in rats, mice, and men [7-10]. Furthermore, 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 [11-13]. Alongside their regulatory capacity, Tregs are characterised by the expression of CD4, CD25 [7], and the highly conserved transcription factor F