Fig. 1.

Gravity gateway reflex. In free-moving mouse (upper panel) with adoptive-transfer EAE, pathogenic CD4+ T cells infiltrate the spinal cord parenchyma at the fifth lumbar (L5) level. This process is triggered by soleus muscle contraction (1) that counteracts gravity to maintain stability and body posture. Stimulated sensory nerves arising from the soleus muscle (2) and entering the L5 spinal cord through dorsal root stimulate sympathetic nerves (3) at the L5 spinal cord level via an unidentified neural circuit (?). This leads to chemokine expression including CCL20 in regional dorsal vessels of the spinal cord (4), establishing an immune cell gateway for migration of pathogenic CD4+ T cells across the BSCB. In tail-suspended mouse (lower panel) with adoptive-transfer EAE, soleus muscle relief from gravitational force (1’) prevents regional activation of sensory- (2’) and sympathetic-nerves (3’), and infiltration of pathogenic CD4+ T cells in the L5 spinal cord (4’). Abbreviations: EAE, experimental autoimmune encephalomyelitis; DRG, dorsal root ganglion; SG, sympathetic ganglion; NE, norepinephrine; BSCB, blood-spinal cord barrier