Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis.

Abstract

Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was γδ T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies.

• Authors: Dongchun Liang, Aijun Zuo, Ronglan Zhao, Hui Shao, Henry J Kaplan, Deming Sun
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 196 Issue 6 Pg. 2646-54 (Mar 15 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 26856700 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Eye Proteins
• Immunologic Factors
• Peptide Fragments
• Receptors, Antigen, T-Cell, gamma-delta
• Retinol-Binding Proteins
• interstitial retinol-binding protein
• Adenosine Deaminase

Topics

• Adenosine Deaminase (administration & dosage)
• Animals
• Autoimmune Diseases (drug therapy, immunology)
• Cells, Cultured
• Eye Proteins (immunology)
• Female
• Humans
• Immunization
• Immunologic Factors (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Animal
• Molecular Targeted Therapy
• Peptide Fragments (immunology)
• Receptors, Antigen, T-Cell, gamma-delta (genetics, metabolism)
• Retinol-Binding Proteins (immunology)
• Th17 Cells (drug effects, immunology)
• Uveitis (drug therapy, immunology)