Gastric epithelial cells directly influence Th17 development and activation during H. pylori infection (152.5)

Abstract

Abstract Gastric epithelial cells (GECs) express class II MHC, act as antigen presenting cells (APCs), and influence CD4+ T cell responses during H. pylori (Hp) infection. Hp, as the major global cause of gastroduodenal ulcers and gastric cancer, elicits GEC responses that include production of proinflammatory cytokines and upregulation of class II MHC and costimulatory molecules that provide signals for CD4+ T cell activation. Recently, the proinflammatory CD4+ phenotype, Th17, was detected in the Hp infected gastric mucosa. Since GECs produce inflammatory cytokines and act as APCs during Hp infection, we hypothesized that the GEC response to Hp infection influences development of Th17 cells in the gastric mucosa. In order to examine this, we investigated Hp-induced GEC production of IL-6 and TGF-β, the cytokines required for Th17 development. These cytokines induced naive CD4+ T expression of RORγt and IL-17A in culture with infected GECs. IL-21, which may play a role in Th17 development, was also found in co-cultures of GECs and CD4+ T cells. Surprisingly, B7-H2 blocking on GECs increased Th17 development. Th17 proliferated in culture and class II MHC was crucial in Th17 proliferation as determined by blocking class II MHC on GECs and measuring CFSE labeled CD4+ T cells gated on RORγt by flow cytometry. These observations suggest a novel mechanism where GECs induce Th17 development and proliferation, which is likely a crucial mechanism in inflammation during Hp infection.