Role of gut inflammation in altering the monocyte compartment and its osteoclastogenic potential in HLA–B27–transgenic rats

Ansalone, C., Utriainen, L., Milling, S. and Goodyear, C. S. (2017) Role of gut inflammation in altering the monocyte compartment and its osteoclastogenic potential in HLA–B27–transgenic rats. Arthritis and Rheumatology, 69(9), pp. 1807-1815. (doi:10.1002/art.40154) (PMID:28511292)

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Abstract

Objective: To investigate the relationship between intestinal inflammation and the central and peripheral innate immune system, in the pathogenesis of HLA-B27 associated spondyloarthritis. Methods: The myeloid compartment of the bone marrow and blood of HLA-B27 transgenic (B27), control HLA-B7 transgenic (B7), and non-transgenic rats were evaluated by flow cytometry. Plasma from rats were assessed by ELISA for CCL2 and IL-1α levels. Rats were treated for 4 weeks with antibiotics and the blood and bone marrow myeloid compartments were evaluated by flow cytometry. The osteoclastogenic potential of bone marrow cells from antibiotic treated rats, in the presence or absence of TNFα, was evaluated in vitro. Results: B27 rats have substantially higher numbers of circulating Lin-CD172a+CD43l° monocytes than control animals, which significantly correlates with higher levels of plasma CCL2. Antibiotic treatment of B27 rats markedly reduced ileitis, plasma CCL2 and IL-1α levels, and the number of bone marrow and blood Lin-CD172a+CD43l° monocytes, which have the greatest in vitro osteoclastogenic potential. Antibiotic treatment also prevented the TNFα-dependent enhancement of osteoclastogenesis in transgenic B27 rats. Conclusions: The microbiota-dependent intestinal inflammation in B27 rats directly drives the systemic inflammatory and bone erosive potential of the monocyte compartment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ansalone, Dr Cecilia and Milling, Professor Simon and Goodyear, Professor Carl and Utriainen, Dr Lotta
Authors: Ansalone, C., Utriainen, L., Milling, S., and Goodyear, C. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Arthritis and Rheumatology
Publisher:Wiley
ISSN:0004-3591
ISSN (Online):1529-0131
Published Online:16 May 2017
Copyright Holders:Copyright © 2017 American College of Rheumatology
First Published:First published in Arthritis and Rheumatology 69(9): 1807-1815
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
569881OSTEOIMMUNE: Unrevealing the Interactions between the Immune System and BoneCarl GoodyearEuropean Commission (EC)FP7 ITN 289150 OSTEOIII -IMMUNOLOGY