| First Author | Smith CJ | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 5 | Pages | 1580-1592 |
| PubMed ID | 29367208 | Mgi Jnum | J:258429 |
| Mgi Id | MGI:6117929 | Doi | 10.4049/jimmunol.1701280 |
| Citation | Smith CJ, et al. (2018) IL-10 Paradoxically Promotes Autoimmune Neuropathy through S1PR1-Dependent CD4(+) T Cell Migration. J Immunol 200(5):1580-1592 |
| abstractText | 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 (S1pr1), a protein important in lymphocyte egress. Additionally, IL-10 stimulation in vitro induced S1pr1 expression in lymph node cells in a STAT3-dependent manner. Together, these results delineate a novel mechanism in which IL-10-induced STAT3 increases S1pr1 expression and CD4(+) T cell migration to accelerate T cell-mediated destruction of peripheral nerves. |
