Selectin Dependence of Allergic Skin Inflammation Is Diminished by Maternal Atopy.

Allergic skin inflammation requires the influx of inflammatory cells into the skin. Extravasation of leukocytes into the skin requires interactions between endothelial selectins and their glycan ligands on the surface of leukocytes. Selectin-ligand formation requires the activity of several glycosyltransferases, including In this report, we tested the importance of for the development of allergic skin inflammation in the Stat6VT transgenic mouse model.

Functions of Smad Transcription Factors in TGF-β1-Induced Selectin Ligand Expression on Murine CD4 Th Cells.

Selectins are carbohydrate-binding adhesion molecules that control leukocyte traffic. Induction of selectin ligands on T cells is controlled primarily by cytokines, including TGF-β1, and requires p38α MAPK, but transcriptional mechanisms that underlie cytokine-driven selectin ligand expression are poorly understood. In this study, we show, using mice with conditional deletions of the TGF-β1-responsive transcription factors Smad2, Smad3, or Smad4, that induction of selectin ligands on CD4 cells in response to TGF-β1 requires Smad4 plus either Smad2 or Smad3.

Diverse inflammatory cytokines induce selectin ligand expression on murine CD4 T cells via p38α MAPK.

Selectins are glycan-binding adhesion molecules that mediate the initial steps of leukocyte recognition of endothelium. Cytokines control numerous aspects of CD4 Th cell differentiation, but how cytokines control the induction of ligands for E- and P-selectin on Th cell subsets remains poorly understood. Among 20 cytokines that affect Th cell differentiation, we identified six that induce expression of selectin ligands on murine CD4 T cells above the low levels associated with TCR engagement: IL-12, IL-18, IL-27, IL-9, IL-25, and TGF-β1.

Impaired selectin-dependent leukocyte recruitment induces T-cell exhaustion and prevents chronic allograft vasculopathy and rejection.

Selectin-selectin ligand interactions mediate the initial steps in leukocyte migration, an integral part of immune responses. Fucosyltransferase-VII (FucT-VII), encoded by Fut7, is essential for biosynthesis of selectin ligands. In an established model of cardiac allograft vasculopathy and chronic rejection, Fut7(-/-) recipients exhibited long-term graft survival with minimal vasculopathy compared with WT controls.

Defining the functional boundaries of the murine α1,3-fucosyltransferase Fut7 reveals a remarkably compact locus.

Fut7 encodes an α1,3-fucosyltransferase critical for biosynthesis of glycan ligands for all three selectins. Consistent with this function, Fut7 expression is limited to hematopoietic cells and high endothelial cells which express selectin ligands. Mechanisms that govern Fut7 expression are poorly defined.