AUTHOR=Zeng Ziyuan , Mao Hanxiao , Lei Qirong , He Yuanmin 

TITLE=IL-7 in autoimmune diseases: mechanisms and therapeutic potential

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1545760

DOI=10.3389/fimmu.2025.1545760

ISSN=1664-3224

ABSTRACT=Interleukin-7 (IL-7) is a pleiotropic cytokine that plays a crucial role in the development, homeostasis, and function of the immune system. Growing evidence has demonstrated that IL-7 is involved in the pathogenesis of various autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D) and multiple sclerosis (MS). This review aims to summarize the current understanding of the role of IL-7 in autoimmune diseases, focusing on its mechanisms of action, implications for disease progression, and potential therapeutic applications. Produced by stromal cells, IL-7 binds to IL-7 receptor (IL-7R) on diverse immune cells. It is crucial for T cell development, survival, and proliferation. In autoimmune diseases, it activates and expands autoreactive T cells and influences B cell function, potentially leading to autoantibody production. The review further delves into the role of IL-7 in different autoimmune diseases. In RA, elevated IL-7/IL-7R promotes memory T cell survival, cytokine production, and influences B cells and monocytes to contribute to inflammation and joint damage. In SLE, elevated soluble form of IL-7R is associated with disease activity, promoting the survival of autoreactive T cells and enhancing the production of pro-inflammatory cytokines. In MS, genetic variations in the IL-7R gene are linked to disease susceptibility, and IL-7 impacts the survival and differentiation of T cell subsets involved in multiple sclerosis pathogenesis. For T1D, IL-7 affects the function of immune cells that attack pancreatic β cells. Given its central role in autoimmune processes, targeting the IL-7/IL-7R axis holds great therapeutic potential. By modulating IL-7 signaling, it may be possible to restore immune tolerance, reduce the activation of autoreactive immune cells, and alleviate disease symptoms. Understanding the complex mechanisms of IL-7 in autoimmune diseases is essential for the development of effective and targeted therapies.