Dissecting the molecular control of immune cell accumulation in the inflamed joint
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 prot...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2022-04-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.151281 |
| _version_ | 1811329646849949696 |
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| author | Catriona T. Prendergast Robert A. Benson Hannah E. Scales Caio Santos Bonilha John J. Cole Iain McInnes James M. Brewer Paul Garside |
| author_facet | Catriona T. Prendergast Robert A. Benson Hannah E. Scales Caio Santos Bonilha John J. Cole Iain McInnes James M. Brewer Paul Garside |
| author_sort | Catriona T. Prendergast |
| collection | DOAJ |
| description | 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 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 rheumatoid arthritis in patient studies, validating the methodology. Focusing on pathways associated with cell migration, adhesion, and movement, we identified genes involved in the retention of immune cells in the inflamed joint, namely junctional adhesion molecule A (JAM-A), and identified a role for such molecules in T cell differentiation in vivo. Thus, using a combination of cell-tracking approaches and murine models of inflammatory arthritis, we identified genes, pathways, and anatomically specific tissue signatures regulating cell migration in a variety of inflamed sites. This skin- and joint-specific data set will be an invaluable resource for the identification of therapeutic targets for arthritis and other inflammatory disorders. |
| first_indexed | 2024-04-13T15:47:29Z |
| format | Article |
| id | doaj.art-5d1175430835444c926fbbd904727585 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T15:47:29Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-5d1175430835444c926fbbd9047275852022-12-22T02:40:55ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-04-0177Dissecting the molecular control of immune cell accumulation in the inflamed jointCatriona T. PrendergastRobert A. BensonHannah E. ScalesCaio Santos BonilhaJohn J. ColeIain McInnesJames M. BrewerPaul GarsideMechanisms 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 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 rheumatoid arthritis in patient studies, validating the methodology. Focusing on pathways associated with cell migration, adhesion, and movement, we identified genes involved in the retention of immune cells in the inflamed joint, namely junctional adhesion molecule A (JAM-A), and identified a role for such molecules in T cell differentiation in vivo. Thus, using a combination of cell-tracking approaches and murine models of inflammatory arthritis, we identified genes, pathways, and anatomically specific tissue signatures regulating cell migration in a variety of inflamed sites. This skin- and joint-specific data set will be an invaluable resource for the identification of therapeutic targets for arthritis and other inflammatory disorders.https://doi.org/10.1172/jci.insight.151281AutoimmunityInflammation |
| spellingShingle | Catriona T. Prendergast Robert A. Benson Hannah E. Scales Caio Santos Bonilha John J. Cole Iain McInnes James M. Brewer Paul Garside Dissecting the molecular control of immune cell accumulation in the inflamed joint JCI Insight Autoimmunity Inflammation |
| title | Dissecting the molecular control of immune cell accumulation in the inflamed joint |
| title_full | Dissecting the molecular control of immune cell accumulation in the inflamed joint |
| title_fullStr | Dissecting the molecular control of immune cell accumulation in the inflamed joint |
| title_full_unstemmed | Dissecting the molecular control of immune cell accumulation in the inflamed joint |
| title_short | Dissecting the molecular control of immune cell accumulation in the inflamed joint |
| title_sort | dissecting the molecular control of immune cell accumulation in the inflamed joint |
| topic | Autoimmunity Inflammation |
| url | https://doi.org/10.1172/jci.insight.151281 |
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