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Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion STED Microscopy
Published on: April 9, 2018
A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation
Isabel Stötzel1, Ann-Kathrin Weier1, Apurba Sarkar2
1Life and Medical Sciences (LIMES) Institute, Immune and Tumor Biology, University of Bonn, Bonn, Germany.
Insights
Extra centrioles in dendritic cells create microtubule organizing centers that impact T cell activation. Optimal centrosome positioning and centriole numbers in antigen-presenting cells are crucial for controlling T cell responses.
Area of Science:
- Immunology
- Cell Biology
- Computational Biology
Background:
- Cellular polarization and centrosome reorientation are vital for immune responses.
- Centrosome repositioning aids T cell activation during immune synapse formation.
- T cells have one centrosome, while antigen-presenting cells amplify centrioles during maturation.
Purpose of the Study:
- To investigate the role of centriole amplification in antigen-presenting cells on immune synapse formation and T cell activation.
- To understand how extra centrioles in dendritic cells influence T cell responses.
Main Methods:
- Combined experimental data with mathematical and computational modeling.
- Studied centrosome integrity, centriole numbers, and configuration in dendritic cells.
- Analyzed T cell activation and immune synapse formation.
Main Results:
- Extra centrioles in dendritic cells form over-active microtubule organizing centers that cluster near the cell center during dendritic cell-T cell interactions.
- Perturbing centrosome integrity or centriole numbers/configuration in dendritic cells impaired T cell activation.
- Demonstrated that dendritic cell centrosome positioning differs from T cells.
Conclusions:
- Centriole amplification in antigen-presenting cells generates over-active microtubule organizing centers.
- Optimal centrosome positioning and centriole numbers in antigen-presenting cells are critical for effective T cell activation and immune response regulation.
Abstract:
Cellular polarization plays a crucial role in regulating immunological processes and is often associated with reorientation of the centrosome. During immune synapse formation, centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells such as dendritic cells amplify centrioles during maturation and immune activation. How centriole amplification in antigen-presenting cells affects immune synapse formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that extra centrioles in dendritic cells form over-active microtubule organizing centers, which cluster during dendritic cell-T cell interactions and, unlike in T cells, localize close to the cell center. Perturbing either centrosome integrity or centriole numbers and configuration in dendritic cells results in impaired T cell activation. Collectively, our results highlight a crucial role for centriole amplification and optimal centrosome positioning in antigen-presenting cells for controlling T cell responses.
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