REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1596686
Immune Cell Senescence in Autoimmunity: Implications for Disease Pathogenesis and Therapeutic Targeting
Provisionally accepted
- Second Affiliated Hospital of Jilin University, Changchun, China
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The senescence of immune cells has also emerged as a key hallmark of immunological dysregulation and chronic inflammation in autoimmunity. Senescent immune cells are irreversibly arrested in the cell cycle, exhibit antimetabolic characteristics, and secrete proinflammatory mediators, all together disrupting immune homeostasis. T cells, B cells, and innate immune subsets, acquire a senescence-associated secretory phenotype (SASP), which initiates tissue damage and sustains continuous inflammation in autoimmune diseases. The accumulation of senescent immune cells undermines immune surveillance, disrupts selftolerance mechanisms, and enhances autoantibody production, all of which contribute to the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Accumulating evidence reveals that metabolic stress, chronic DNA damage, and persistent antigenic exposure in inflammatory microenvironments induce immune cell senescence. Such senescent condition more aggressively promotes disease pathogenesis by compromising antigen presentation, disrupting cytokine signaling, and weakening the function of regulatory T cells (Tregs).Targets of senolytic drugs, SASP inhibitors, monoclonal antibodies (mAbs), and CAR T cell therapy currently have the potential to accelerate autoimmune pathology. These treatments would be directed specifically against the selective elimination or reprogramming of senescent cells to restore immune homeostasis. This review examines the mechanistic relationships between autoimmune development and immune cell senescence, as well as recent advancements in senescence-directed therapy. Understanding these pathways can provide new insights into autoimmune pathogenesis and inform future therapeutic approaches to immune cell aging.
Keywords: immune cell senescence, autoimmune disease, senescence-associated secretory phenotype, senolytics, Monoclonal antibody
Received: 20 Mar 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Yin, He, Li and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuan Gao, Second Affiliated Hospital of Jilin University, Changchun, China
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