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Synapse
April 23, 20260 citationsOpen Access

Distinct dendritic cell cytoskeletal programs dictate synapse architecture and CD8+ T cell fate.

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CCCamille ClamagirandCRChristoph RatswohlMSMarc W. Schmid

Key Points

  • The aim is to understand how dendritic cell structure impacts the activation and fate of CD8+ T cells at the immunological synapse.
  • Utilized bone marrow-derived dendritic cells (BMDCs) to identify subpopulations based on synapse morphology.
  • Characterized dendritic cell synapses as 'firework' or 'pancake' based on CD70 expression levels.
  • Analyzed the impact of dendritic cell synapse architecture on T cell differentiation and function.
  • CD70high BMDCs create spiky 'firework' synapses and promote terminally differentiated Tc1 effector cells.
  • CD70low BMDCs generate smooth 'pancake' synapses and lead to memory T cells with a Tc17-like profile.
  • The structural characteristics of dendritic cell synapses are pivotal in determining T cell fate.

Abstract

Dendritic cell activation of CD8+ T cells at the immunological synapse is critical for immunity, but the structural organization of the dendritic cell side and its impact on T cell fate remain poorly defined. Using bone marrow-derived dendritic cells (BMDCs) as a model, we describe two stable subpopulations distinguished by their capacity to form morphologically distinct synapses. We demonstrate that this architectural divergence is governed by the differential expression of the co-stimulatory molecule CD70: CD70high BMDCs form spiky "firework" synapses driven by a filopodia-based cytoskeletal program, while CD70low BMDCs form smooth "pancake" synapses. This structural dichotomy functionally dictates T cell programming. CD70high dendritic cells prime potent, terminally differentiated Tc1 effector cells. In contrast, IL-6-secreting CD70low dendritic cells generate memory T cells with a Tc17-like functional profile and robust recall capacity. Our work reveals that DC synapse architecture is a key determinant of T cell fate, linking the physical organization of the cell to distinct immunological outcomes.

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Cite This Study

Clamagirand et al. (2026) studied this question.

synapsesocial.com/papers/69e9b8d485696592c86ebd18https://doi.org/10.48620/97119
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