Authors
Rabia Nabi, Chien-Wei Lin, Yu Wang, Ashley E Ciecko, Bardees M Foda, Yushu Wang, Amber Drewek, Scott M Lieberman, William M Ridgway, Yi-Guang Chen
Published in
The Journal of experimental medicine. Volume 223. Issue 8. Aug 03, 2026. Epub Jul 07, 2026.
Abstract
CD137 is expressed in a subset of Foxp3+ regulatory CD4 T cells (Tregs), but its immunoregulatory role is not fully defined. Due to alternative splicing that removes the transmembrane domain-encoding exon, CD137 exists in both membrane and soluble forms. We investigated the function of CD137 in Foxp3+ Tregs using the NOD mouse model of type 1 diabetes (T1D). Foxp3+ Treg-specific deletion of CD137 reduced circulating soluble CD137 and accelerated T1D development, driven by heightened clonal expansion and differentiation of effector T cells in pancreatic islets. CD137 deficiency in Foxp3+ Tregs reduced their frequency in islets and impaired their differentiation toward a suppressive phenotype. Restoring soluble CD137 in Foxp3+ Tregs lacking its membrane form reduced islet T cell activation and mitigated T1D acceleration without altering the accumulation of suppressive Foxp3+ Tregs. Our results indicate that both soluble and membrane forms of CD137 expressed by Foxp3+ Tregs are critical for immunoregulation, and they independently restrain T1D development.
PMID:
42412561
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.
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