Aging and T cell Senescence in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is the most common acquired chronic autoimmune neuropathy and occurs more frequently in the aged, with a peak incidence in those 70-79 years of age. How aging predisposes to peripheral nervous system (PNS) autoimmunity, however, is unclear. Early aging-associated changes include the acquisition of T cell immunosenescence, a dysfunctional, pro- inflammatory state that can lead to the spread of senescence to neighboring cell types. Our data demonstrate an increased burden of senescent T cells in patients and mice with CIDP, compared to age-matched controls. Moreover, our data suggest that peripheral nerve-infiltrating CD4+ T cells actively signal to adjacent PNS cell types, including Schwann cells, in a mouse model of CIDP. Thus, in this R21 proposal, we will test the hypothesis that senescence-associated CD4+ T cells predispose to PNS autoimmunity by inducing neighboring Schwann cells to acquire a senescent, dysfunctional state. In Aim 1, we will test how adoptive transfer of senescent T cells into an immunodeficient mouse recipients alters Schwann cell phenotype in the peripheral nerves of recipients. We will also assess whether conditioned media from senescent T cells of CIDP patients will induce senescence in a human Schwann cell line. In Aim 2, we will examine how disease protection is conferred by a senomorphic agent, ruxolitinib, in mice with CIDP and through the use of CIDP patient samples. Completion of these Aims are important steps toward a more comprehensive understanding of autoimmune mechanisms in CIDP and may point to the use of senomorphic therapies for the benefit of CIDP patients. Project Number: 1R21NS146827-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Maureen Su | Institution: UNIVERSITY OF CALIFORNIA LOS ANGELES, LOS ANGELES, CA | Award Amount: $236,250 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 CN-Q (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11294895