The Spleen Negatively Regulates the Acute Phase of Experimental Autoimmune Encephalomyelitis in Mice

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), is characterized by neuroinflammation and neurodegeneration. Both the innate and adaptive immune systems, with effector cells such as B and T lymphocytes, are critically involved in the pathogenesis of MS. Existing disease-modifying therapies have limited efficacy against progressive MS, and there is a strong need to identify new drug targets. Investigating how peripheral organs influence lymphocyte dynamics in the pathogenesis of MS may provide new insights for identifying novel therapeutic targets. The spleen is the largest secondary lymphoid organ with several immunological roles, including the activation of naïve CD4⁺ T cells. In this study, we investigated the contribution of the spleen to experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS, in splenectomized (SPX) mice. SPX mice exhibited more severe EAE symptoms and larger demyelinated areas than sham-operated controls. SPX mice showed enhanced T-helper type 1 (Th1) differentiation at the onset of the disease and increased activation of ionized calcium-binding adapter molecule 1 (Iba1)-immunopositive myeloid cells at the peak of the disease. Thus, we inferred that the spleen plays an important role in the pathology of EAE by regulating microglial activation and macrophage infiltration during the disease's acute phase.