Therefore, our data suggest that astrocytes activated by cell-to-cell contact, particularly with mast cells, may exacerbate the development of neurodegenerative disease including demyelization, such as MS, due to enhancement of cytokine receptor expression on astrocytes caused by inflammatory cytokine secretion as well as interaction of CD40 with CD40L in vitro and in mouse EAE model. Here, CD40LG is linked to neurodegenerative disease.