Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis.

The adoptive transfer of myelin-reactive T cells into wild-type hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoimmune encephalomyelitis (EAE), as opposed to brainstem inflammation and ataxia, which characterize disease in IFN-γRKO hosts (atypical EAE). In this article, we show that atypical EAE correlates with preferential upregulation of CXCL2 in the brainstem, and is driven by CXCR2-dependent recruitment of neutrophils. In contrast, conventional EAE is associated with upregulation of CCL2 in the spinal cord, and is driven by recruitment of monocytes via a partially CCR2-dependent pathway. This study illustrates how regional differences in chemokine expression within a target organ shape the spatial pattern and composition of autoimmune infiltrates, leading to disparate clinical outcomes.