HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling - Summary - MDSpire

HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling

  • By

  • Elsa M. Reyes-Reyes

  • Dhanalakshmi Chinnasamy

  • Michael D. Trial

  • Fernando Fernandez

  • Vincent D. Nguyen

  • Qianying He

  • Angel-Grace Leslie

  • Jessica Begay

  • Jessica Triplett

  • David Bradford

  • Carolina Figueroa

  • Jean P. Wiegand

  • Kathleen E. Rodgers

  • June 16, 2026

  • 0 min

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Objective:

To investigate how HLA-DRB1*15:01 expression modulates age- and sex-dependent neuroimmune processes within the central nervous system.

Key Findings:
  • HLA mice exhibited age- and sex-dependent cognitive impairment, particularly in aged females.
  • HLA-DRB1*15:01 expression led to increased microglial immune-associated changes and oxidative stress.
  • Disruption of hippocampal axonal and myelin organization was observed in aged HLA mice.
  • Increased accumulation of CD4+ T cells and NK1.1+CD3+ NKT cells was noted, especially in females.
  • Endothelial activation was marked by elevated ICAM-1 and E-selectin expression.
  • Hippocampal cytokine profiling showed selective sex-biased alterations.
Interpretation:

HLA-DRB1*15:01 drives a coordinated neuroinflammatory program linked to cognitive dysfunction, immune changes, and oxidative stress, with a heightened impact in females.

Limitations:
  • The study was conducted in a mouse model, which may not fully replicate human neuroimmune processes.
  • The effects of reproductive cycling stages in females were not extensively analyzed.
Conclusion:

HLA-DRB1*15:01 confers vulnerability to chronic neuroinflammation during aging, particularly affecting females.

Original Source(s)

HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling

  • by Elsa M. Reyes-Reyes, Dhanalakshmi Chinnasamy, Michael D. Trial, Fernando Fernandez, Vincent D. Nguyen, Qianying He, Angel-Grace Leslie, Jessica Begay, Jessica Triplett, David Bradford, Carolina Figueroa, Jean P. Wiegand, Kathleen E. Rodgers

  • June 16, 2026

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