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Limited effect of indolamine 2,3-dioxygenase expression and enzymatic activity on lupus-like disease in b6.Nba2 mice

Lookup NU author(s): Dr Lei Huang, Professor Andrew Mellor

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2019 Davison, Liu, Huang, Carroll, Mellor and Jørgensen.B6.Nba2 mice spontaneously develop a lupus-like disease characterized by elevated levels of serum anti-nuclear autoantibody (ANA) immune complexes and constitutive type I interferon (IFNα) production. During disease progression, both plasmacytoid dendritic cells (pDCs) and antibody secreting plasma cells accumulate in spleens of B6.Nba2 mice. Indoleamine 2,3-dioxygenase (IDO) has been suggested to play a role in several autoimmune diseases including in the MRL/lpr model of mouse lupus-like disease; however, it remains unknown if IDO is involved in disease development and/or progression in other spontaneous models. We show here that IDO1 protein and total IDO enzymatic activity are significantly elevated in lupus-prone B6.Nba2 mice relative to B6 controls. IDO1 expression was restricted to PCs and SignR1+ macrophages in both strains, while significantly increased in B6.Nba2-derived SiglecH+ (SigH+) pDCs. Despite this unique expression pattern, neither pharmacologic inhibition of total IDO nor IDO1 gene ablation altered serum autoantibody levels, splenic immune cell activation pattern, or renal inflammation in B6.Nba2 mice. Interestingly, IDO pharmacologic inhibition, but not IDO1 deficiency, resulted in diminished complement factor C’3 fixation to kidney glomeruli, suggesting a possible therapeutic benefit of IDO inhibition in SLE patients with renal involvement.


Publication metadata

Author(s): Davison LM, Liu JC, Huang L, Carroll TM, Mellor AL, Jorgensen TN

Publication type: Article

Publication status: Published

Journal: Frontiers in Immunology

Year: 2019

Volume: 10

Issue: 2017

Online publication date: 27/08/2019

Acceptance date: 08/08/2019

Date deposited: 02/10/2019

ISSN (electronic): 1664-3224

Publisher: Frontiers Research Foundation

URL: https://doi.org/10.3389/fimmu.2019.02017

DOI: 10.3389/fimmu.2019.02017


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