| Autor: |
Danzer, Claudia, Koller, Anna, Baier, Julia, Arnold, Harald, Giessler, Claudia, Opoka, Robert, Schmidt, Stephanie, Willers, Maike, Mihai, Sidonia, Parsch, Hans, Wirtz, Stefan, Daniel, Christoph, Reinhold, Annegret, Engelmann, Swen, Kliche, Stefanie, Bogdan, Christian, Hoebe, Kasper, Mattner, Jochen |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Popis: |
TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp-76 on iNKT-cell biology. Compared to B6 controls, slp-76ace/ace mice carrying a missense mutation (Thr428Ile) within the SH2-domain of slp-76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduction in iNKT cells was observed in the livers and spleens of ADAP-deficient mice. Like ADAP−/− iNKT cells, slp-76ace/ace iNKT cells were characterized by enhanced CD11b expression, correlating with an impaired induction of the TCR immediate-early gene Nur77 and a decreased adhesion to ICAM-1. Furthermore, CD11b-intrinsic effects inhibited cytokine release, concanavalin A-mediated inflammation, and iNKT-cell accumulation in the liver. Unlike B6 and ADAP−/− mice, the expression of the transcription factors Id3 and PLZF was reduced, whereas NP-1-expression was enhanced in slp-76ace/ace mice. Blockade of NP-1 decreased the recovery of iNKT cells from peripheral lymph nodes, identifying NP-1 as an iNKT-cell-specific adhesion factor. Thus, slp-76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP-dependent and -independent mechanisms |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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