The intestinal immune system discriminates between tolerance toward the commensal microflora and robust responses to pathogens. Maintenance of this critical balance is attributed to mucosal dendritic cells (DCs) residing in organized lymphoid tissue and dispersed in the subepithelial lamina propria. In situ parameters of lamina propria DCs (lpDCs) remain poorly understood. Here, we combined conditional cell ablation and precursor-mediated in vivo reconstitution to establish that lpDC subsets have distinct origins and functions. CD103(+) CX(3)CR1(-) lpDCs arose from macrophage-DC precursors (MDPs) via DC-committed intermediates (pre-cDCs) through a Flt3L growth-factor-mediated pathway. CD11b(+) CD14(+) CX(3)CR1(+) lpDCs were derived from grafted Ly6C(hi) but not Ly6C(lo) monocytes under the control of GM-CSF. Mice reconstituted exclusively with CX(3)CR1(+) lpDCs when challenged in an innate colitis model developed severe intestinal inflammation that was driven by graft-derived TNF-alpha-secreting CX(3)CR1(+) lpDCs. Our results highlight the critical importance of the lpDC subset balance for robust gut homeostasis.

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Our data suggest a significant association between age and serum ALT activity. This association is not a simple linear correlation, but rather an inverted-U-like relation. Thus, when interpreting the laboratory results of a subject suspected of liver disease, age should probably be taken into account. Larger-scale studies are needed to better characterize this issue.

This study documents that hospitalized IBD patients with CDAD have low rate of endoscopic pseudomembranes, which is not accounted for by the use of immunosuppressant drugs. IBD patients with CDAD and discernable pseudomembranes more commonly present with fever, but their clinical outcome is similar to patients without pseudomembranes.