p38MAPK/SGK1 signaling regulates macrophage polarization in experimental autoimmune encephalomyelitis

Area of Science:

• Neuroimmunology
• Cellular Biology
• Molecular Signaling

Background:

• Multiple sclerosis (MS) involves central nervous system inflammation and demyelination.
• The p38 mitogen-activated protein kinase (MAPK)/serum- and glucocorticoid-inducible protein kinase 1 (SGK1) pathway is implicated in MS pathogenesis.
• The role of this pathway in macrophage polarization in MS remains unclear.

Purpose of the Study:

• To investigate the role of p38MAPK/SGK1 signaling in macrophage polarization.
• To determine the effect of this pathway on experimental autoimmune encephalomyelitis (EAE) severity.
• To explore therapeutic potential in MS models.

Main Methods:

• Utilized an EAE mouse model for multiple sclerosis.
• Investigated IL-4 induced M2 macrophage polarization in vitro.
• Employed adeno-associated virus (AAV) vectors for gene knockdown (sh-p38, sh-SGK1).
• Assessed macrophage polarization and EAE severity following gene knockdown.

Main Results:

• p38MAPK/SGK1 signaling is essential for IL-4-induced M2 macrophage polarization.
• Chitin-induced M2 macrophage polarization reduced EAE severity.
• Knockdown of p38 or SGK1 using AAV vectors reversed these effects.
• p38MAPK/SGK1 signaling blockade exacerbated EAE.

Conclusions:

• p38MAPK/SGK1 signaling promotes M2 macrophage polarization.
• M2 macrophages induced by this pathway ameliorate EAE severity.
• Targeting p38MAPK/SGK1 signaling may offer a therapeutic strategy for MS.