IL-21 is required for maintaining mucosal Th1 and Th17 responses during Helicobacter pylori infection

Carbo, A., R. Hontecillas, M.K. Washignton, R. Chatuverdi, D. Olivares-Villagomez, K.T. Wilson, J. Bassaganya-Riera and H.S. Algood (2013) IL-21 is required for maintaining mucosal Th1 and Th17 responses during Helicobacter pylori infection, American Association of Immunologists Annual Meeting, Honolulu HI

CD4+ T cells play a major role in the modulation of immune responses at the gastric mucosa during Helicobacter pylori infection. The relative contributions of CD4+ T cell subsets to gastritis and control of H. pylori colonization and clearance are not completely understood. Expression of IL-21, which is produced by a number of T cell subsets, increases during H. pylori infection. To elucidate the mechanisms of action of IL-21 in effector and regulatory CD4+ T cells during H. pylori infection, we combined computational modeling of CD4+ T cell differentiation and in vivo challenge studies in mice. Our computational modeling predicted activated production of IFN and IL-17 by IL-21, and the expression of T-bet, RORt and phosphorylation of STAT3. To investigate the role of IL-21 in vivo, we infected IL-21-/- and wild-type mice with H. pylori SS1, and assessed colonization, gastric inflammation, cellular infiltration and cytokine profiles in the gastric mucosa. During chronic infection, IL-21-/- mice had higher H. pylori colonization, less gastritis and reduced expression of inflammatory cytokines and chemokines. Moreover, H. pylori infected IL-21-/- mice had reduced levels of CD4+ T cell specific RORt and T-bet when compared to infected wild-type mice. Our results indicate that IL-21contributes to the control of infection and severity of gastritis, suggesting a role for induction of gastritis in response to H. pylori through activation of both Th17 and Th1 effector responses.