@Article{biocell.2026.073956,
AUTHOR = {Jingfei Shi, Yi Ding, Hui Lu},
TITLE = {sIL-2RA Exacerbates Multiple Sclerosis by Activating Microglia and Upregulating Fc Receptors on Microglia},
JOURNAL = {BIOCELL},
VOLUME = {50},
YEAR = {2026},
NUMBER = {3},
PAGES = {0--0},
URL = {http://www.techscience.com/biocell/v50n3/66708},
ISSN = {1667-5746},
ABSTRACT = { <b>Objective:</b> Multiple 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. <b>Methods:</b> Female 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. <b>Results:</b> sIL-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 (<i>p</i> < 0.001). Inhibiting FcγR or PI3K-Akt reduced oligodendrocyte damage. <b>Conclusion:</b> sIL-2Rα exacerbates MS by activating microglia via the PI3K-Aktaxis, promoting ADCC and demyelination. Targeting this pathway may offer novel therapeutic strategies for MS.},
DOI = {10.32604/biocell.2026.073956}
}