Immunoregulatory functions of KLRG1 cadherin interactions are dependent on forward and reverse signaling
| Autor: | Cindy Banh, Laurent Brossay, Céline Fugere |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Immunoprecipitation T-Lymphocytes Blotting Western Immunology Biology Lymphocyte Activation Polymerase Chain Reaction Biochemistry Mice chemistry.chemical_compound Cell Adhesion Animals Lectins C-Type Receptors Immunologic Cell adhesion Receptor Immunobiology Cadherin Tyrosine phosphorylation Dendritic Cells Cell Biology Hematology Dendritic cell Cadherins Flow Cytometry Transmembrane protein Cell biology Mice Inbred C57BL chemistry Cytokines Signal transduction Signal Transduction |
| Zdroj: | Blood. 114:5299-5306 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-06-228353 |
| Popis: | KLRG1 is an inhibitory receptor expressed on a subset of mature T and NK cells. Recently, E-, N-, and R-cadherin have been identified as ligands for KLRG1. Cadherins are a large family of transmembrane or membrane-associated glycoproteins that were thought to only bind specifically to other cadherins to mediate specific cell-to-cell adhesion in a Ca2+-dependent manner. The consequences of cadherin KLRG1 molecular interactions are not well characterized. Here, we report that the first 2 extracellular domains of cadherin are sufficient to initiate a KLRG1-dependent signaling. We also demonstrate that KLRG1 engagement inhibits cadherin-dependent cellular adhesion and influences dendritic cell secretion of inflammatory cytokines, thereby exerting immunosuppressive effects. Consistent with this, engagement of cadherin by KLRG1 molecule induces cadherin tyrosine phosphorylation. Therefore, KLRG1/cadherin interaction leads to the generation of a bidirectional signal in which both KLRG1 and cadherin activate downstream signaling cascades simultaneously. Taken together, our results provide novel insights on how KLRG1 and E-cadherin interactions are integrated to differentially regulate not only KLRG1+ cells, but also E-cadherin–expressing cells, such as dendritic cells. |
| Databáze: | OpenAIRE |
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