Mechanosensing by Peyer's patch stroma regulates lymphocyte migration and mucosal antibody responses.

Fibroblastic reticular cells (FRCs) and their specialized collagen fibers termed 'conduits' form fundamental structural units supporting lymphoid tissues. In lymph nodes, conduits are known to transport interstitial fluid and small molecules from afferent lymphatics into the nodal parenchyma. However, the immunological contributions of conduit function have remained elusive.

Stromal infrastructure of the lymph node and coordination of immunity.

The initiation of adaptive immune responses depends upon the careful maneuvering of lymphocytes and antigen into and within strategically placed lymph nodes (LNs). Non-hematopoietic stromal cells form the cellular infrastructure that directs this process. Once regarded as merely structural features of lymphoid tissues, these cells are now appreciated as essential regulators of immune cell trafficking, fluid flow, and LN homeostasis.

Intestinal epithelial expression of TNFAIP3 results in microbial invasion of the inner mucus layer and induces colitis in IL-10-deficient mice.

Tumor necrosis factor-induced protein 3 (TNFAIP3; also known as A20) negatively regulates NF-κB and MAPK signals to control inflammatory responses. TNFAIP3 also protects against TNF-induced cell death. Intestinal epithelial cell (IEC) expression of TNFAIP3 improves barrier function and tight junction integrity and prevents dextran sulfate sodium (DSS)-induced IEC death and colitis.

Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis.

Intestinal epithelial cells (IEC) maintain gastrointestinal homeostasis by providing a physical and functional barrier between the intestinal lumen and underlying mucosal immune system. The activation of NF-κB and prevention of apoptosis in IEC are required to maintain the intestinal barrier and prevent colitis. How NF-κB activation in IEC prevents colitis is not fully understood.

TNFAIP3 maintains intestinal barrier function and supports epithelial cell tight junctions.

Tight junctions between intestinal epithelial cells mediate the permeability of the intestinal barrier, and loss of intestinal barrier function mediated by TNF signaling is associated with the inflammatory pathophysiology observed in Crohn's disease and celiac disease. Thus, factors that modulate intestinal epithelial cell response to TNF may be critical for the maintenance of barrier function. TNF alpha-induced protein 3 (TNFAIP3) is a cytosolic protein that acts in a negative feedback loop to regulate cell signaling induced by Toll-like receptor ligands and TNF, suggesting that TNFAIP3 may play a role in regulating the intestinal barrier.

hPepT1 transports muramyl dipeptide, activating NF-kappaB and stimulating IL-8 secretion in human colonic Caco2/bbe cells.

Background And Aims: Bacterial proteoglycan-derived muramyl dipeptide (MDP) activates the intracellular NOD2/CARD15 gene product. How intestinal epithelial cells take up MDP is poorly understood. We hypothesized that the intestinal apical di-/tripeptide transporter, hPepT1, transports MDP, thereby activating downstream pathways similar to nuclear factor kappa B (NF-kappaB).