title: Regulation and migratory role of P-selectin ligands during intestinal inflammation.
abstract: Dendritic cells from mesenteric lymph nodes (MLN) can convert retinal to retinoic acid (RA), which promotes induction of the gut-specific homing receptor α4β7. In contrast, priming within peripheral lymph nodes leads to upregulation of E- and P-selectin ligands (E- and P-lig). Apart from its α4β7 promoting effect, RA was shown to suppress E- and P-lig induction in vitro. However, enhanced frequencies of P-lig(+) CD4(+) T cells were reported during intestinal inflammation. To understand this contradiction, we first determined whether location of intestinal inflammation, that is, ileitis or colitis, affects P-lig induction. Both conditions promoted P-lig expression on CD4(+) T cells; however, P-lig expressed on T cells facilitated Th1 cell recruitment only into the inflamed colon but not into inflamed small intestine induced by oral Toxoplasma gondii infection. A majority of P-lig(+)CD4(+) T cells found within MLN during intestinal inflammation co-expressed α4β7 confirming their activation in the presence of RA. Mesenteric P-lig(+)CD4(+) cells co-expressed the 130 kDa isoform of CD43 which requires activity of core 2 (beta)1,6-N-acetyl-glycosaminyltransferase-I (C2GlcNAcT-I) suggesting that C2GlcNAcT-I contributes to P-lig expression under these conditions. To test whether inflammatory mediators can indeed overrule the inhibitory effect of RA on P-lig expression we stimulated CD4(+) T cells either polyclonal in the presence of IL-12 and IFNγ or by LPS-activated MLN-derived dendritic cells. Both conditions promoted P-lig induction even in the presence of RA. While RA impeded the induction of fucosyltransferase-VII it did not affect IL-12-dependent C2GlcNAcT-I induction suggesting that C2GlcNAcT-I can support P-lig expression even if fucosyltransferase-VII mRNA upregulation is dampened.
authors: Deutsches Rheumaforschungszentrum, Berlin, Germany.
authors: Ute
authors: U
authors: Hoffmann
authors: Matthias
authors: M
authors: Pink
authors: Uta
authors: U
authors: Lauer
authors: Markus M
authors: MM
authors: Heimesaat
authors: Caroline
authors: C
authors: Winsauer
authors: Andrei
authors: A
authors: Kruglov
authors: Kerstin
authors: K
authors: Schlawe
authors: Claudia
authors: C
authors: Leichsenring
authors: Oliver
authors: O
authors: Liesenfeld
authors: Alf
authors: A
authors: Hamann
authors: Uta
authors: U
authors: Syrbe
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005759:Gastroenteritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016023:Integrins / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018417:Th1 Cells / Q000502:physiology; D014212:Tretinoin / Q000502:physiology
chemical_list: D016023:Integrins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; C071777:integrin alpha4beta7; D014212:Tretinoin
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