@article{Shi2026, 
author = {Jingfei Shi and Yi Ding and Hui Lu},
title = {sIL-2RA Exacerbates Multiple Sclerosis by Activating Microglia and Upregulating Fc Receptors on Microglia},
year = {2026},
journal = {BIOCELL},
volume = {50},
number = {3},
pages = {7},
keywords = {Multiple sclerosis, soluble interleukin-2 receptor α, microglial activation, phosphatidylinositol 3-kinase–protein kinase B signaling (PI3K-Akt) signaling pathway, antibody-dependent cellular cytotoxicity},
url = {https://www.sciopen.com/article/10.32604/biocell.2026.073956},
doi = {10.32604/biocell.2026.073956},
abstract = {ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Soluble interleukin-2 receptor alpha (sIL-2Rα) has been implicated in MS pathogenesis, but its mechanisms remain unclear. This study investigates how sIL-2Rα exacerbates MS by modulating microglial activation and antibody-dependent cellular cytotoxicity (ADCC) in an experimental autoimmune encephalomyelitis (EAE) mouse model.MethodsFemale C57BL/6J mice were induced with EAE and treated with sIL-2Rα. Clinical symptoms, histopathology, and molecular changes were analyzed. Microglial activation was assessed via immunohistochemistry, Western blot, and RNA sequencing. In vitro, ADCC-mediated oligodendrocyte injury was evaluated using Fc receptor inhibition and PI3K-Akt pathway blockade.ResultssIL-2Rα accelerated EAE onset and severity, increasing microglial M1 polarization and CNS inflammation. RNA-seq revealed PI3K-Akt pathway activation, upregulating Fc receptors (FcγR) on microglia, which enhanced ADCC against oligodendrocytes (p < 0.001). Inhibiting FcγR or PI3K-Akt reduced oligodendrocyte damage.ConclusionsIL-2Rα exacerbates MS by activating microglia via the PI3K-Aktaxis, promoting ADCC and demyelination. Targeting this pathway may offer novel therapeutic strategies for MS.}
}