IL-10 Paradoxically Promotes Autoimmune Neuropathy through S1PR1-Dependent CD4 + T Cell Migration

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a debilitating condition caused by autoimmune demyelination of peripheral nerves. CIDP is associated with increased IL-10, a cytokine with well-described anti-inflammatory effects. However, the role of IL-10 in CIDP is unclear. In this study, we demonstrate that IL-10 paradoxically exacerbates autoimmunity against peripheral nerves. In IL-10-deficient mice, protection from neuropathy was associated with an accrual of highly activated CD4 T cells in draining lymph nodes and absence of infiltrating immune cells in peripheral nerves. Accumulated CD4 T cells in draining lymph nodes of IL-10-deficient mice expressed lower sphingosine-1-phosphate receptor 1 ( ), a protein important in lymphocyte egress. Additionally, IL-10 stimulation in vitro induced expression in lymph node cells in a STAT3-dependent manner. Together, these results delineate a novel mechanism in which IL-10-induced STAT3 increases expression and CD4 T cell migration to accelerate T cell-mediated destruction of peripheral nerves.