Inhaltszusammenfassung

Although IL-10 promotes a regulatory phenotype of CD11c(+) dendritic cells and macrophages in vitro, the role of IL-10 signaling in CD11c(+) cells to maintain intestinal tolerance in vivo remains elusive. To this aim, we generated mice with a CD11c-specific deletion of the IL-10 receptor alpha (Cd11c(cre)Il10ra(fl/fl)). In contrast to the colon, the small intestine of Cd11c(cre)Il10ra(fl/fl) mice exhibited spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes and lam...Although IL-10 promotes a regulatory phenotype of CD11c(+) dendritic cells and macrophages in vitro, the role of IL-10 signaling in CD11c(+) cells to maintain intestinal tolerance in vivo remains elusive. To this aim, we generated mice with a CD11c-specific deletion of the IL-10 receptor alpha (Cd11c(cre)Il10ra(fl/fl)). In contrast to the colon, the small intestine of Cd11c(cre)Il10ra(fl/fl) mice exhibited spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes and lamina propria T cells, associated with elevated levels of T cell-derived IFN gamma and IL-17A. Whereas naive mucosal T-cell priming was not affected and oral tolerance to ovalbumin was intact, augmented T-cell function in the lamina propria was associated with elevated numbers of locally dividing T cells, expression of T-cell attracting chemokines and reduced T-cell apoptosis. Upon stimulation, intestinal IL-10Ra deficient CD11c(+) cells exhibited increased activation associated with enhanced IL-6 and TNFa production. Following colonization with Helicobacter hepaticus Cd11c(cre)Il10ra(fl/fl) mice developed severe large intestinal inflammation characterized by infiltrating T cells and increased levels of Il17a, Ifng, and Il12p40. Altogether these findings demonstrate a critical role of IL-10 signaling in CD11c(+) cells to control small intestinal immune homeostasis by limiting reactivation of local memory T cells and to protect against Helicobacter hepaticus-induced colitis.» weiterlesen» einklappen

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DDC Sachgruppe:
Medizin