Dissecting the molecular control of immune cell accumulation in the inflamed joint

Prendergast, C. T., Benson, R. A. , Scales, H. E. , Bonilha, C. S., Cole, J. J., McInnes, I. , Brewer, J. M. and Garside, P. (2022) Dissecting the molecular control of immune cell accumulation in the inflamed joint. JCI Insight, 7(7), e151281. (doi: 10.1172/jci.insight.151281) (PMID:35192549) (PMCID:PMC9057592)

Abstract

Mechanisms governing entry and exit of immune cells into, and out of, inflamed joints, remain poorly understood. We sought herein to identify the key molecular pathways regulating such migration. Using murine models of inflammation in conjunction with mice expressing a photoconvertible fluorescent protein we characterized the migration of cells from joints to draining lymph nodes (LN) and performed RNA-seq analysis on isolated cells, identifying genes associated with migration and retention. We further refined the gene list to those specific for joint inflammation. RNA-seq data revealed pathways and genes previously highlighted as characteristic of RA in patient studies, validating the methodology. Focusing on gene regulatory pathways associated with cell migration, adhesion and movement, we identified genes involved in the retention of immune cells in the inflamed joint, namely JAM-A, and identified a role for such molecules in T cell differentiation in vivo.Thus, using a combination of novel cell tracking approaches and murine models of inflammatory arthritis we have identified genes, pathways and anatomically specific tissue signatures regulating cell migration in a variety of inflamed sites. This unique skin and joint specific dataset will be an invaluable resource for the identification of novel therapeutic targets for arthritis and other inflammatory disorders.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Prendergast, Dr Catriona and Cole, Mr John and Benson, Dr Robert and Brewer, Professor James and Garside, Professor Paul and Scales, Dr Hannah and Bonilha, Mr Caio
• Authors: Prendergast, C. T., Benson, R. A., Scales, H. E., Bonilha, C. S., Cole, J. J., McInnes, I., Brewer, J. M., and Garside, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: JCI Insight
• Publisher: American Society for Clinical Investigation
• ISSN: 2379-3708
• ISSN (Online): 2379-3708
• Published Online: 22 February 2022
• Copyright Holders: Copyright © 2022 Prendergast et al.
• First Published: First published in JCI Insight 7(7): e151281
• Publisher Policy: Reproduced under a Creative Commons License