Analysis of Mouse Dendritic and Antigen presenting cell and Mouse autoimmune and Inflammatory Response

ABSTRACT: Antigen presenting cells (APC) express receptors recognizing microbes and regulating immune responses by binding to corresponding ligands on immune cells. Having discovered a novel inhibitory pathway triggered by ligation of DC-HIL on APC to a heparin/heparan sulfate-like saccharide of syndecan-4 on activated T cells, we posited DC-HIL can recognize microbial pathogens in a similar manner. We showed soluble recombinant DC-HIL to bind the dermatophytes Trichophyton rubrum and Microsporum audouinii, but not several bacteria nor Candida albicans. Dermatophyte binding was inhibited completely by the addition of heparin. Because DC-HIL contains an immunoreceptor tyrosine-based activation motif (ITAM)-like intracellular sequence, we questioned whether its binding to dermatophytes can induce tyrosine phosphorylation in dendritic cells (DC). Culturing DC with T. rubrum (but not with C. albicans pseudohyphae) induced phosphorylation of DC-HIL, but not when the tyrosine residue of the ITAM-like sequence was mutated to phenylalanine. To examine the functional significance of such signaling on DC, we cross-linked DC-HIL with mAb (surrogate ligand), which not only induced tyrosine phosphorylation but also upregulated expression of 23 genes among 662 genes analyzed by gene-array, including genes for profilin-1, Marcksl-1, C/EBP, LOX-1, IL-beta and TNF-alpha. This cross-linking also upregulated expression of the activation markers CD80/CD86 and heightened APC capacity of DC to activate syngeneic T cells. Our findings support a dual role for DC-HIL; inhibition of adaptive immunity following ligation of syndecan-4 on activated T cells, and induction of innate immunity against dermatophytic fungi.

ORGANISM(S): Mus musculus

PROVIDER: GSE17699 | GEO | 2009/08/19

SECONDARY ACCESSION(S): PRJNA118405

REPOSITORIES: GEO