Senescent CD4 T cells drive age-associated autoimmunity in mice and humans
Targeting senescent immune cells with fisetin or ruxolitinib reduced disease features and protected mice against autoimmune peripheral nerve damage.
bioRxiv : the preprint server for biology · McCarthy EC et al. · Paper published 22 Sep 2026
In human patients with chronic inflammatory demyelinating polyneuropathy and in mice with CIDP-like disease, researchers found elevated numbers of immunosenescent CD4+ T cells. These cells displayed higher SA-beta-gal activity, increased p21 expression, and upregulated CD153. They also exhibited a senescence-associated secretory phenotype, decreased proliferation, resistance to apoptosis, and a stronger ability to incite neuropathy. The preprint study tested two targeted treatments. The senolytic compound fisetin reduced the pathogenic capacity of these CD4+ T cells. Furthermore, the senomorphic drug ruxolitinib, which suppresses the senescence-associated secretory phenotype, protected mice against autoimmune demyelination. Together, the findings demonstrate that senescent CD4+ T cells play a key role in age-associated peripheral nervous system autoimmunity.
Why it matters
The study directly links cellular senescence in the immune system to late-onset autoimmune disease. It highlights senolytics and senomorphics as potential therapeutic approaches for age-related autoimmune pathology.
Caveats
The findings are reported in a preprint that has not yet completed peer review. Therapeutic efficacy against autoimmune demyelination was established in mice rather than clinical trials.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Age-associated Autoimmunity Driven by T cell Immunosenescence
McCarthy EC, Seyedsadr M, Bang MF et al.
bioRxiv : the preprint server for biology · 22 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Animals
- Status
- Preprint
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