| First Author | Wei J | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32118582 | Mgi Jnum | J:291571 |
| Mgi Id | MGI:6443081 | Doi | 10.7554/eLife.51102 |
| Citation | Wei J, et al. (2020) A novel role for lipoxin A4 in driving a lymph node-eye axis that controls autoimmunity to the neuroretina. Elife 9:e51102 |
| abstractText | The eicosanoid lipoxin A4 (LXA4) has emerging roles in lymphocyte-driven diseases. We identified reduced LXA4 levels in posterior segment uveitis patients and investigated the role of LXA4 in the pathogenesis of experimental autoimmune uveitis (EAU). Immunization for EAU with a retinal self-antigen caused selective downregulation of LXA4 in lymph nodes draining the site of immunization, while at the same time amplifying LXA4 in the inflamed target tissue. T cell effector function, migration and glycolytic responses were amplified in LXA4-deficient mice, which correlated with more severe pathology, whereas LXA4 treatment attenuated disease. In vivo deletion or supplementation of LXA4 identified modulation of CC-chemokine receptor 7 (CCR7) and sphingosine 1- phosphate receptor-1 (S1PR1) expression and glucose metabolism in CD4(+) T cells as potential mechanisms for LXA4 regulation of T cell effector function and trafficking. Our results demonstrate the intrinsic lymph node LXA4 pathway as a significant checkpoint in the development and severity of adaptive immunity. |
