TY  - EJOU
AU  - Shi, Jingfei 
AU  - Ding, Yi 
AU  - Lu, Hui 

TI  - sIL-2RA Exacerbates Multiple Sclerosis by Activating Microglia and Upregulating Fc Receptors on Microglia
T2  - BIOCELL

PY  - 2026
VL  - 50
IS  - 3
SN  - 1667-5746

AB  -  <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.
KW  - Multiple sclerosis; soluble interleukin-2 receptor α; microglial activation; phosphatidylinositol 3-kinase–protein kinase B signaling (PI3K-Akt) signaling pathway; antibody-dependent cellular cytotoxicity

DO  - 10.32604/biocell.2026.073956