Immunohistochemical and flow cytometric analyses of HB-EGF production by cortical and spinal cord astrocytes throughout the course of EAE confirmed these observations, collectively demonstrating that both cortical and spinal cord astrocytes upregulate HB-EGF during peak stages and lose its expression during LSW (Fig. 2d–g and Extended Data Fig. 2i,j), aligning with our findings in patients with CIS and RRMS. Here, HBEGF is linked to relapsing-remitting multiple sclerosis.