Human monocytes and macrophages regulate immune tolerance via integrin αvβ8–mediated TGFβ activation
Open accessAbstract
Monocytes are crucial immune cells involved in regulation of inflammation either directly or via differentiation into macrophages in tissues. However, many aspects of how their function is controlled in health and disease are not understood. Here we show that human blood monocytes activate high levels of the cytokine TGFβ, a pathway that is not evident in mouse monocytes. Human CD14+, but not CD16+, monocytes activate TGFβ via expression of the integrin αvβ8 and matrix metalloproteinase 14, which dampens their production of TNFα in response to LPS. Additionally, when monocytes differentiate into macrophages, integrin expression and TGFβ-activating ability are maintained in anti-inflammatory macrophages but down-regulated in pro-inflammatory macrophages. In the healthy human intestine, integrin αvβ8 is highly expressed on mature tissue macrophages, with these cells and their integrin expression being significantly reduced in active inflammatory bowel disease. Thus, our data suggest that integrin αvβ8–mediated TGFβ activation plays a key role in regulation of monocyte inflammatory responses and intestinal macrophage homeostasis.
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Mice lacking αvβ6 integrin are protected in mouse models of lung, kidney, and biliary fibrosis.
“Mice lacking the αvβ6 integrin are protected in mouse models of lung, kidney and biliary fibrosis90,98–102”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [98]
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Self-citation
- Authors
- Kelly, A., Gunaltay, S., McEntee, C. P., Shuttleworth, E. E., Smedley, C., Houston, S. A., Fenton, T. M., Levison, S., Mann, E. R., & Travis, M. A.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK 1
- Manchester Royal Infirmary (GB)
- Corresponding author
- Travis, Mark A.
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2018-10-24
- Volume
- 215
- Issue
- 11
- Pages
- 2725-2736
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC6219736
- OpenAlex
- W2898513675
- Cited by
- 124
- References
- 64
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 19 · 2023: 17 · 2022: 10 · 2021: 22 · 2020: 21 · 2019: 13 · 2018: 2
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- Funders
- Manchester Collaborative Centre for Inflammation Research
- Medical Research Council (MR/M00242X/1)
- Wellcome Trust (209741/Z/17/Z, 108746/Z/15/Z, 203128/Z/16/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- monocytes, macrophages, integrin αvβ8, immune tolerance, MMP-14, CD14+ monocytes, CD16+ monocytes, TNF-α, lipopolysaccharide, monocyte differentiation, intestinal macrophages, inflammatory bowel disease
- MeSH terms
- Adolescent, Adult, Aged, Female, Humans, Immune Tolerance, Intestines, Macrophages, Male, Middle Aged, Monocytes, Tumor Necrosis Factor-alpha, Inflammatory Bowel Diseases, Integrins, Transforming Growth Factor beta
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