Pathologic T cell immunosenescence drives the development of age-associated autoimmune peripheral neuropathy

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-βGal activity and higher CDKN1A expression. These senescence associated T cells express multiple senescence associated secretory phenotype (SASP) factors (IFN-γ, TNF-α, TGF-β, 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. Competing Interest Statement The authors have declared no competing interest.