Proinflammatory Th2 Cytokines Induce Production of Thymic Stromal Lymphopoietin in Human Colonic Epithelial Cells

Abstract

Taken together, as in human allergic diseases, an inflammatory Th2 condition in the mucosal lesions of UC patients may trigger increased TSLP expression by IECs, resulting in exacerbation of UC.

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

“…TSLP expression was also found in gastric mucosal lesions from patients with Helicobacter pylori-induced chronic gastritis and H. pylori colonization-induced TSLP production in gastric epithelial cells (27). In the intestine, mRNA expression of TSLP was overexpressed in patients with ulcerative colitis, and proinflammatory cytokines induced overexpression of TSLP in colonic epithelial cells (32,33). Therefore, TSLP can be expressed in the intestinal tract throughout the esophagus, stomach, and small and large intestines, both in humans and mice, suggesting that TSLP is involved in various immune responses in the gastrointestinal tract.…”

“…TSLP overexpression is thought to be involved in H. pylori-induced chronic gastritis with formation of B cell follicles (18,27). In addition, mRNA expression of TSLP was significantly reduced in patients with Crohn's disease, whereas TSLP was overexpressed in patients with ulcerative colitis (32,33). Taking these results together, although TSLP is deeply involved in the pathophysiology of some allergic or Th2-dependent inflammatory conditions, its primary role in physiological conditions of the gastrointestinal tract may be to maintain intestinal immune homeostasis, including regulation of autoimmunity.…”

Intestinal IL-17 Expression in Canine Inflammatory Bowel Disease

“…Cytokines have important roles in the regulation of the mucosal immune system of dogs as well as humans. In human, CD is associated with a Th1 response mainly driven by IL-12 and IFNγ [21], while UC is driven by Th2 cytokines, such as IL-4, IL-5, and IL-13 [27]. In contrast, dogs with IBD express with a mixture of both Th1 and Th2 cytokines, including IL2, IL4, IL5, IL10, IL12, IFNγ, TNFα, and TGFβ, in intestinal mucosa [17].…”

Helicobacter pylori Promotes the Production of Thymic Stromal Lymphopoietin by Gastric Epithelial Cells and Induces Dendritic Cell-Mediated Inflammatory Th2 Responses

“…Th2 responses triggering B-cell activation appear to be involved in the development of lymphoid aggregates with germinal centers. However, molecular mechanisms to induce Th2 responses triggering B-cell activation are not clear.In humans, an epithelial-cell-derived cytokine, thymic stromal lymphopoietin (TSLP), activates CD11c ϩ myeloid dendritic cells (DCs), and activated DCs strongly upregulate the expression of costimulatory molecules, such as CD80 and CD86 (23,38,43,44). TSLP-activated DCs promote CD4 ϩ T cells to differentiate into inflammatory Th2 cells that produce interleukin-4 (IL-4), IL-5, IL-13, and tumor necrosis factor alpha (TNF-␣) while downregulating IL-10 and gamma interferon (IFN-␥) (23, 44).…”

“…Samples of mucosa in biopsy specimens were obtained from inflamed gastric mucosae in three patients with Helicobacter-induced follicular gastritis (male/female ratio, 1/2; mean age [range], 37.3 [32][33][34][35][36][37][38][39][40][41][42][43][44] years). Samples of healthy controls were taken from three patients with duodenal ulcers (male/female ratio, 2/1; mean age [range], 37.7 [35][36][37][38][39][40][41][42][43] years) in whom the absence of inflammation had been histopathologically confirmed.…”