title: 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.
authors: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Hisayo
authors: H
authors: Nishiura
authors: Masahiro
authors: M
authors: Kido
authors: Nobuhiro
authors: N
authors: Aoki
authors: Satoru
authors: S
authors: Iwamoto
authors: Ryutaro
authors: R
authors: Maruoka
authors: Aki
authors: A
authors: Ikeda
authors: Tsutomu
authors: T
authors: Chiba
authors: Steven F
authors: SF
authors: Ziegler
authors: Norihiko
authors: N
authors: Watanabe
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005756:Gastritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000276:immunology / Q000473:pathology; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D007136:Immunoglobulins; D053762:Interleukin-12 Subunit p40; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D007371:Interferon-gamma; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse