Research Project
Grant-in-Aid for Scientific Research (C)
In this study, we tried to elucidate pathophysiological roles of human thymic stromal lymphopoietin (TSLP) in inflammatory bowel diseases and we obtained the following results. (1) Dendritic cells (DCs) activated by TSLP, expressed in the epithelial cells of mucosal lymphoid tissues, can induce a robust expansion of autologous T_H2 memory cells. The maintenance and homeostatic expansion of T_H2 memory cells mediated by TSLP-activated DCs require the self peptide-major histocompatibility complex, costimulatory molecules, and particularly, the interactions between OX40 and OX40 ligand. In addition to indirectly action on T-cell proliferation through DC activation, TSLP directly promotes CD4^+ T-cell proliferation. Moreover, CD8^+ T cells activated by T cell receptor stimulation expresse TSLP receptor, and that TSLP directly enhances proliferation of activated CD8^+ cells. (2) Although Helicobacter bacteria colonize in the stomach and induce chronic active gastritis, Peyer's patches in th … More e small intestine have an important role in Helicobacter-specific local and systemic humoral and cell-mediated immunity, including the development of Helicobacter-induced gastritis. In addition, Helicobacter triggers human gastric epithelial cells to produce TSLP and DC-attracting chemokines and epithelial cell-conditioned DCs expresses high levels of costimulatory molecules and triggers naive CD4 T cells to produce high levels of the inflammatory Th2 cytokines. (3) TNF-a triggers human colonic epithelial cells to produce TSLP and IL-4 enhances TNF-a-inducing TSLP expression in colonic epithelial cells. Myeloid DCs responded to a combination of TSLP and TLR3-ligand(L) to upregulate expression of functional TSLP receptor and TLR3. Although TSLP alone did not induce IL-23 production by DCs, TLR3-L alone primed DCs for production of IL-23, and a combination of TSLP and TLR3-L primed DCs for further production of IL-23. DCs activated by a combination of TSLP and TLR3-L primed naive CDC T cells to produce IL-17 and IL-22, together with high levels of Th2 cytokines and TNF-α. Less
All 2008 2007 2006
All Journal Article (23 results) (of which Peer Reviewed: 10 results) Presentation (9 results)
Gastroenterology 134
Pages: 642-643
Helicobacter 12
Pages: 486-497
Int Immunol 19
Pages: 435-446
10020110345
J Immunol 178
Pages: 6720-6724
Int. Immunol 19
J. Immunol 178
Journal of Immunology 178
Pages: 193-219
International Immunology. 19・4
Gastrointestinal Endoscopy. 65・3
Pages: 545-547
American Journal Gastroenterology. 101・12
Pages: 2878-2883
Am J Gastroenterol 101
Blood 107
Pages: 3617-3623
Immunity 24
Pages: 827-838
Gut 55
Pages: 607-615
Am. J. Gastroenterol 101
Blood. 107・9
Immunity. 24・6
