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

Abstract

Thymic stromal lymphopoietin (TSLP), mainly produced by epithelial cells, activates a variety of cell types, including dendritic cells, mast cells, T cells, and B cells. It is involved in the pathogenesis of allergic inflammation in the lung, skin, and gastrointestinal tract. In addition, TSLP promotes Th2-type intestinal immunity against helminth infection and regulates Th1-type inflammation in a mouse model of colitis, suggesting that it plays crucial roles in intestinal immune homeostasis. Although autoimmune gastritis (AIG), mediated by inflammatory Th1 responses, develops in the gastric mucosa, it is not clear whether TSLP is involved in regulating these responses in AIG. The aim of this study was to examine the roles of TSLP in the development of AIG. Because BALB/c mice thymectomized 3 d after birth (NTx mice) develop AIG, we used this model to test the role of TSLP in the development of AIG. We found that in AIG-bearing mice, TSLP was expressed in the inflamed stomach and that the serum anti-parietal cell Ab levels in neonatal thymectomized TSLPR-deficient mice (NTx-TSLPR−/− mice) were significantly elevated over those in NTx-TSLPR+/+ mice. In addition, NTx-TSLPR−/− mice exhibited an earlier onset of AIG than that observed in NTx-TSLPR+/+ mice. The rapid development of AIG in NTx-TSLPR−/− mice resulted in more aggressive CD4+ T cell infiltration and more severe loss of parietal and chief cells in the progression phase of AIG, accompanied by enhanced production of IL-12/23p40 and IFN-γ. Taken together, these data suggested that TSLP negatively regulates the development of AIG.

Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice

“…In addition, the distribution of TSLP in the thymus was similar to that in keratin 5 þ medullary thymic epithelial cells (mTECs), suggesting that only mTECs express TSLP in the thymus. It has been reported that altered TSLPR expression could lead to reduced Tregs in multiple sclerosis [20] and increased Th1 immune responses in autoimmune gastritis [50]. Indeed, the reduced TSLP expression in atherosclerotic mice in the present study is consistent with less TSLP expression in severely obese men with compared with without the metabolic syndrome [51], in which the precise mechanism has not been elucidated.…”

Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer

“…Other studies have reported the expression and secretion of TSLP from cancer cells in various malignancies among breast, lung, and pancreatic cancers. In both humans and mice, TSLP mRNA expression was found in the intestines, stomach, and esophagus [46]. TSLP mRNA was significantly overexpressed in the intestines of mice and patients with ulcerative colitis, as well as in inflamed esophageal tissues of patients with eosinophilic esophagitis [45,[47][48][49][50][51].…”

The Biology of Thymic Stromal Lymphopoietin (TSLP)

“…Additionally, loss of TSLP signaling in a mouse model of autoimmune gastritis resulted in more severe disease (Nishiura et al, 2012). Although the impact of TSLP on colitis in mice appears more complex (Taylor et al, 2009; Reardon et al, 2011), this supports a model in which loss of TLSP, which can block TH1/TH17 responses, leads to increased inflammation.…”