A novel role for lipoxin A4 in driving a lymph node-eye axis that controls autoimmunity to the neuroretina.
Jessica WeiMary J MattapallilReiko HoraiYingyos JittayasothornArnav P ModiH Nida SenKarsten GronertRachel R CaspiPublished in: eLife (2020)
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.
Keyphrases
- lymph node
- end stage renal disease
- neoadjuvant chemotherapy
- dendritic cells
- dna damage
- sentinel lymph node
- juvenile idiopathic arthritis
- chronic kidney disease
- newly diagnosed
- binding protein
- ankylosing spondylitis
- poor prognosis
- rheumatoid arthritis
- radiation therapy
- multiple sclerosis
- high resolution
- peripheral blood
- risk assessment
- prognostic factors
- squamous cell carcinoma
- peritoneal dialysis
- combination therapy
- human health
- type iii
- optical coherence tomography