A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation

TL;DR

This study shows that extra centrioles in antigen-presenting cells help activate T cells by forming active microtubule centers.

Contribution

The study reveals how centriole amplification in antigen-presenting cells influences T cell activation through centrosome dynamics.

Findings

Dendritic cells amplify centrioles during immune activation.

Extra centrioles form active microtubule organizing centers near the cell center.

Disrupting centriole numbers or positioning impairs T cell activation.

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.

Centrosome dynamics play a central role in immune regulation. Here, the authors demonstrate that centrosome integrity as well as centriole numbers and spatial organisation emerge as critical determinants of effective T cell responses.

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