Mucosal IL-17 Immunity in Disease - With Special Reference to Inflammatory Bowel Disease
Year: 2012
Type: dissertation
Abstract: T cells are CD4 lymphocytes participating in cell-mediated immunity, and play a critical role in immune-mediated diseases. T cells divide further into subclasses such as Th1, Th2, and Th17 that participate in mucosal immunity responses caused by extracellular pathogens and also play a role in autoimmune diseases. Th17 cells produce cytokines called the interleukin-17 family (IL-17). Regulatory CD4+ T cells marked by CD4, CD25, and forkhead box P3 (FOXP3), contribute to maintaining tolerance and regulating immune responses to antigens. This doctoral thesis studies the role of IL-17 type of immunity in intestinal inflammation in Crohn s disease, ulcerative colitis, celiac disease, and type I diabetes (T1D). In particular, the study explores the balance between effector and regulatory T cells in active and inactive Crohn s disease in adults, as well as in pediatric patients with Crohn s disease and ulcerative colitis. Furthermore, the investigation focuses on the effect of anti-TNF-α treatment on the effector and regulatory T cells in Crohn s disease in adults. Adult patients with Crohn s disease had higher numbers of intestinal IL-17+ and FOXP3+ cells than did control subjects, both before and after the anti-TNF-α treat-ment. Intestinal interferon-γ and IL-17 mRNA expression was higher in Crohn s disease and remained elevated after anti-TNF-α treatment, although the treatment improved intestinal balance between IL-17+ effector and regulatory T cells. In Crohn s disease, mRNA expression of IL-17A, IL-6, and FOXP3 was increased. Fecal IL-17 concentration showed increase in patients with active disease. IL-17 enhanced the IL-8 and TNF-α response of the epithelial cell line to lipopolysaccha-ride in vitro. The findings suggest that activation of the IL-17 axis is fundamentally connected to the etiology of Crohn s disease and may represent the basis for the relapsing nature of the disease. In pediatric patients, IL-17, IL-22, IL-6, and FOXP3+ mRNA up-regulation and increase in the number of IL-17+ and FOXP3+ cells existed in inflammatory bowel disease. Activation of the IL-17/IL-22 axis and up-regulation of FOXP3 occurred both in pediatric Crohn s disease and ulcerative colitis, indicating shared immuno-logical aberrancy. In pediatric patients with untreated celiac disease, the mucosal expression of IL-17 and FOXP3 transcripts were elevated as compared with TGA-negative reference children, children with potential celiac disease, gluten-free diet-treated children with celiac disease, or children with T1D. Enhanced spontaneous secretion of IL-1β, IL-6, and IL-17 occurred in biopsy specimens from patients with untreated celiac disease. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17, howev-er, could serve as a biomarker for the development of villous atrophy and active celiac disease.
Source: Työväentutkimus Vuosikirja
Author: Veera Hölttä
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1147264373