2. Academic Validation
  3. Social status impacts T-cell responses through synapse strength in the prefrontal cortex

Social status impacts T-cell responses through synapse strength in the prefrontal cortex

  • Cell Res. 2026 Mar 23. doi: 10.1038/s41422-026-01235-7.
Hui Xiong # 1 2,  Daniel Amado-Ruiz # 1 2,  Tessa R Lodder 1 2,  Mireille Toebes 3,  Ton N Schumacher 3,  Hailan Hu 4,  Helmut W Kessels 5 6
Affiliations

Affiliations

  • 1 Department of Cellular and Circuit Neuroscience, Swammerdam Institute for Life Sciences, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
  • 2 The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
  • 3 Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • 4 Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. huhailan@zju.edu.cn.
  • 5 Department of Cellular and Circuit Neuroscience, Swammerdam Institute for Life Sciences, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands. h.kessels@uva.nl.
  • 6 The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. h.kessels@uva.nl.
  • # Contributed equally.
PMID: 41866615 DOI: 10.1038/s41422-026-01235-7
Abstract

Social status affects health by influencing the capacity of the immune system to respond to Infection and disease. However, the neuronal mechanisms that explain how social status causes individual differences in immunity are unknown. In this study, we observed that among social groups of four male mice, those ranked second in the hierarchy displayed, on average, superior T-cell responses upon vaccination. The greater T-cell responses in second-ranked mice were dependent on synaptic communication ability in the brain. The brain circuits that control position in the social hierarchy are beginning to emerge, with the dorsomedial prefrontal cortex (dmPFC) as a central player. We found that selectively increasing the strength of dmPFC synapses or increasing the activity of dmPFC neurons was sufficient to boost antigen-specific T-cell percentages in response to vaccination. These findings reveal a causal link between the dmPFC and the peripheral immune system, enriching our understanding of the origin of health problems caused by social inequality.

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