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 (Cd11ccreIl10rafl/fl). In contrast to the colon, the small intestine of Cd11ccreIl10rafl/fl mice exhibited spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes and lamina propria T cells, associated with elevated levels of T cell-derived IFNγ 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 Cd11ccreIl10rafl/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.

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doi.org/10.18632/oncotarget.8337, hdl.handle.net/1765/95981
Oncotarget
Department of Immunology

Girard-Madoux, M., Ober-Blöbaum, J., Costes, L.M.M. (Léa M.M.), Kel, J., Lindenbergh-Kortleve, D., Brouwers-Haspels, I., … Clausen, B. (2016). IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestine. Oncotarget, 7(22), 32015–32030. doi:10.18632/oncotarget.8337