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A macrophage marker, siglec‐1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type i interferons and toll‐like receptor agonists
Abstract
Objective: Microarray analyses of peripheral blood leukocytes have shown that patients with systemic lupus erythematosus express increased levels of type I interferon (IFN)–regulated genes. In this study we examined gene expression by peripheral blood mononuclear cells (PBMCs) from patients with systemic sclerosis (SSc) to better understand the dysregulation of the immune system in this disease. Methods: PBMC gene expression was analyzed by microarray and confirmed by real‐time polymerase chain reaction (PCR). Surface protein expression of Siglec‐1 was analyzed by flow cytometry in PBMCs from healthy control subjects and patients with SSc, and in control PBMCs that were cultured in vitro with Toll‐like receptor (TLR) agonists. Results: SSc patients showed increased expression of a cluster of IFN‐regulated genes, including Siglec‐1 (CD169, sialoadhesin). This result was verified and extended by real‐time PCR, showing that a subset of the SSc patients expressed strikingly increased levels of Siglec‐1 messenger RNA (mRNA). Flow cytometry of PBMCs from SSc patients and healthy controls showed increased Siglec‐1 surface protein expression, which was restricted to CD14+ monocytes. In vitro studies showed that type I IFN and certain TLR agonists, including TLR‐7 and TLR‐9, induced Siglec‐1 mRNA and protein expression. Moreover, TLR induction of surface Siglec‐1 was shown to be type I IFN–dependent. Increased numbers of Siglec‐1+ cells were observed by immunohistochemistry in the skin of SSc patients compared with healthy controls. Conclusion: Increased expression of Siglec‐1 in circulating SSc monocytes and tissue macrophages suggests that type I IFN–mediated activation of monocytes occurs in SSc, possibly through TLR activation of IFN secretion. These observations indicate a potential role for type I IFN–activated monocyte/macrophages in the pathogenesis of SSc.
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Cited by
Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities
Bhattacharyya, S., Wei, J., & Varga, J. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.149 · Cited by 381
Transforming growth factor β—at the centre of systemic sclerosis
Lafyatis, R. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.137 · Cited by 332
Self-citationToll-Like Receptor Pathways in Autoimmune Diseases
Chen, J.-Q., Szodoray, P., & Zeher, M. (2016) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-015-8473-z · Cited by 315
Huttner, A., Dayer, J.-A., Yerly, S., Combescure, C., Auderset, F., Desmeules, J., Eickmann, M., Finckh, A., Goncalves, A. R., Hooper, J. W., et al. (2015) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(15)00154-1 · Cited by 272
Puryear, W. B., Akiyama, H., Geer, S. D., Ramirez, N. P., Yu, X., Reinhard, B. M., & Gummuluru, S. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003291 · Cited by 181
Metadata
- Authors
- York, M. R., Nagai, T., Mangini, A. J., Lemaire, R., van Seventer, J. M., & Lafyatis, R.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2007-02-27
- Volume
- 56
- Issue
- 3
- Pages
- 1010-1020
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2094596462
- Cited by
- 327
- References
- 0
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: A macrophage marker, siglec‐1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type i interferons and toll‐like receptor agonists. https://app.cochat.ai/papers/10.1002/art.22382
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- York, M. R., Nagai, T., Mangini, A. J., Lemaire, R., van Seventer, J. M., & Lafyatis, R. (2007). A macrophage marker, siglec‐1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type i interferons and toll‐like receptor agonists. Arthritis & Rheumatism. https://doi.org/10.1002/art.22382
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