Vision Science Program, University of California, Berkeley, Berkeley, United States; Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United States
Mary J Mattapallil
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United States
Reiko Horai
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United States
Yingyos Jittayasothorn
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United States
Arnav P Modi
School of Optometry, University of California, Berkeley, Berkeley, United States
H Nida Sen
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United States
Vision Science Program, University of California, Berkeley, Berkeley, United States; School of Optometry, University of California, Berkeley, Berkeley, United States; Infectious Disease and Immunity Program, University of California, Berkeley, Berkeley, United States
Rachel R Caspi
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United States
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.
