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Laquinimod arrests development of experimental autoimmune uveitis (EAU) and inhibits related immune processes, in the context of altered gut microbiota

Biying Xu, Xiuzhi Jia, Jihong Tang, Rachel R Caspi and Igal Gery
J Immunol May 1, 2020, 204 (1 Supplement) 150.18;
Biying Xu
1NEI, NIH
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Xiuzhi Jia
1NEI, NIH
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Jihong Tang
1NEI, NIH
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Rachel R Caspi
1NEI, NIH
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Igal Gery
1NEI, NIH
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Abstract

EAU is an animal model for autoimmune uveitis in humans and is used to study mechanisms and potential therapeutics for this blinding disease. Here, we tested the immunosuppressive efficacy of Laquinimod (LAQ), a potent AhR (aryl hydrocarbon receptor) ligand on development of EAU.

C57BL/6J mice were challenged for EAU with 300ug of the uveitogenic antigen, IRBP 651–670 and were treated from day 0 or day 7, relative to immunization, with 25mg/Kg LAQ, or PBS, by oral gavage. EAU progression was monitored by fundus examination and confirmed by histology on day 14 post immunization (p.i.). Treatment with LAQ from day 0 p.i. completely prevented EAU development and inhibited proliferation and production of pro-inflammatory cytokines to peptide 651–670. Treatment with LAQ from day 7 p.i. also significantly inhibited the development of EAU and cellular immune responses, but to a lesser degree than in day 0 mice. In contrast to its inhibitory effect on pro-inflammatory processes, LAQ treatment increased the proportions of T-regulatory FoxP3+CD4+ T cells in treated mice, as compared to the control group.

Metagenomic analyses revealed that immunized mice treated with LAQ had altered composition of gut microbiota when compared with PBS controls, with an increased population of Bifidobacteriaceae, and decreased Clostridaceae 1, Deflubiitaleaceae and Anaeroplasmataceae bacteria.

Our results demonstrate that LAQ, a water-soluble AhR ligand, is a potent inhibitor of EAU development and exerts its effect primarily during the inductive phase of the disease. The connection of the observed changes in gut microbiota to its inhibitory effects on disease is under investigation.

  • Copyright © 2020 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 204, Issue 1 Supplement
1 May 2020
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Laquinimod arrests development of experimental autoimmune uveitis (EAU) and inhibits related immune processes, in the context of altered gut microbiota
Biying Xu, Xiuzhi Jia, Jihong Tang, Rachel R Caspi, Igal Gery
The Journal of Immunology May 1, 2020, 204 (1 Supplement) 150.18;

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Laquinimod arrests development of experimental autoimmune uveitis (EAU) and inhibits related immune processes, in the context of altered gut microbiota
Biying Xu, Xiuzhi Jia, Jihong Tang, Rachel R Caspi, Igal Gery
The Journal of Immunology May 1, 2020, 204 (1 Supplement) 150.18;
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Print ISSN 0022-1767        Online ISSN 1550-6606