Interplay of leukocytes, regulatory T cells, and interleukin-17+ cells in the pathogenesis of canine chronic ulcerative stomatitis

Abstract

Objectives Canine chronic ulcerative stomatitis (CCUS) is a spontaneously occurring inflammatory disease of the oral mucosa. Lesions present as numerous, often bilaterally symmetric deep ulcerations of the nonkeratinized tissues, with an erosive, lichenoid, or pseudomembranous appearance. An immune pathogenesis is suspected, although not yet proven. A description of the clinical oral findings, histologic appearance, and select leukocyte cell populations was reported in 2017. Additionally, we determined that FoxP3 and moderate numbers of CD3–/interleukin (IL)-17+ cells were present in affected tissues. We proposed a similarity to human oral lichen planus. Study Design In this study, we extended these observations by examining 24 dogs with clinical evidence of CCUS through the use of tissue-based special stains, immunohistochemistry (IHC), immunofluorescence (IF), confocal microscopy, and direct immunofluorescence (DIF). We also used this battery of diagnostic modalities to examine tissues obtained from dogs with periodontitis and oral neoplasia and compared these results with those from dogs with CCUS. We hypothesized that dogs with CCUS would exhibit a spectrum of pathologic changes and phenotypes of infiltrating leukocytes that would inform lesion pathogenesis, prognosis, and treatment and would differ from periodontitis and oral tumors. Results Our results confirmed that all CCUS leukocyte cell types are present in higher numbers than in controls. Differences were found between CCUS lesions in male and female subjects, among histologic variants, and according to periodontal disease stage. FoxP3 was present in all lesions on IHC and variably present on IF. IL-17+ cells were frequent, and the majority were CD3–/IL-17+. DIF results did not support an autoantibody autoimmune disease process. Conclusions Leukocyte cell types and IL-17+ cells are important in this chronic disease process. This investigation adds to the scant body of literature on T-helper cell type 17 (Th17)/IL-17 involvement in canine idiopathic inflammatory and/or autoimmune diseases. As such, CCUS may represent a nonmouse model for other spontaneously occurring inflammatory diseases in canines and humans.