Pathologic T cell immunosenescence drives the development of age-associated autoimmune peripheral neuropathy
McCarthy, E. C.; Seyedsadr, M.; Bang, M. F.; Pham, C. L. H.; Bustillos, C.; Salladay-Perez, I.; Whitmire, J. K.; Lechner, M. G.; Shieh, P.; Covarrubias, A. J.; Su, M. A.
Show abstract
While certain autoimmune conditions occur commonly in the young, others are more frequent in the aged. A striking example is chronic inflammatory demyelinating polyneuropathy (CIDP), an autoimmune disease of peripheral nerves that occurs at a peak decade of onset of 70-79 years. How aging predisposes to autoimmunity, however, remains unclear. In CIDP patients, we identified an expanded population of T cells that exhibit hallmark senescence features, including increased SA-{beta}Gal activity and higher CDKN1A expression. These senescence associated T cells express multiple senescence associated secretory phenotype (SASP) factors (IFN-{gamma}, TNF-, TGF-{beta}, IL21, Spp1) and demonstrated an enhanced capacity for inciting neuropathy in a CIDP mouse model. Notably, SASP suppression by a clinically available senomorphic therapy dampened senescence features in peripheral nerves and protected mice against neuropathy. Together, these findings delineate a key role for T cells exhibiting a pro-inflammatory SASP in predisposing to age-associated autoimmune disease.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genetically perturbed myelin as a risk factor for neuroinflammation-driven axon degeneration 96%
- Senescent-like microglia limit remyelination through the senescence associated secretory phenotype 96%
- Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells 94%
Similar papers in this journal
Similar papers in this journal
- Aging-related cell type-specific pathophysiologic immune responses that exacerbate disease severity in aged COVID-19 patients 94%
- Single-cell RNA sequencing identifies accumulation of Fcgr2b+ virtual memory like CD8 T cells with cytotoxic and inflammatory potential in aged mouse white adipose tissue 94%
- Conclusive Identification of Senescent T Cells Reveals Their Abundance in Aging Humans 93%
Similar papers in this journal
- Single Cell Deconstruction of Muscle Stem Cell Heterogeneity During Aging Reveals Sensitivity to the Neuromuscular Junction 95%
- JAK inhibition decreases the autoimmune burden in Down syndrome 94%
- Fine-tuning spatial-temporal dynamics and surface receptor expression support plasma cell-intrinsic longevity 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.