LFA-1 activation in NK cells and their subsets: influence of receptors, maturation, and cytokine stimulation
The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The bindi...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
18 January 2017
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| In: |
The journal of immunology
Year: 2017, Jahrgang: 198, Heft: 5, Pages: 1944-1951 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.1601004 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.4049/jimmunol.1601004 Verlag, kostenfrei, Volltext: http://www.jimmunol.org/content/198/5/1944 
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| Verfasserangaben: | Doris Urlaub, Kristine Höfer, Martha-Lena Müller, and Carsten Watzl |
| Zusammenfassung: | The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations. Short-term stimulation of freshly isolated NK cells with cytokines, such as IL-15, IL-12, or IL-18, does not activate LFA-1 but increases the responsiveness of the cells to subsequent receptor stimulation. Different NK cell subsets vary in their ability to induce LFA-1 binding activity after activating receptor stimulation. Interestingly, the NK cell subsets that are more mature and possess higher cytotoxic potential also show the highest activation of LFA-1, which correlated with the expression of the small calcium-binding protein S100A4. Our data suggest that regulation of LFA-1 is one reason for the different activity of NK cells during differentiation. |
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| Beschreibung: | Gesehen am 15.10.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.1601004 |