Annexin-1 modulates T-cell activation and differentiation
Open accessAbstract
Annexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity; however, its potential actions in the modulation of adaptive immunity have never been explored. Although inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. This effect was paralleled by increased nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFATs), and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor (TCR)–induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells; in the collagen-induced arthritis model, treatment of mice with annexin-1 during the immunization phase exacerbated signs and symptoms at disease onset. Consistent with these findings, blood CD4+ cells from patients with rheumatoid arthritis showed a marked up-regulation of annexin-1 expression. Together these results demonstrate that annexin-1 is a molecular “tuner” of TCR signaling and suggest this protein might represent a new target for the development of drugs directed to pathologies where an unbalanced Th1/Th2 response or an aberrant activation of T cells is the major etiologic factor.
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Several molecules demonstrated strong co-expression with IL1R1, including CD53, CD9, and ANXA1.
“Several molecules demonstrated strong co-expression with IL1R1, among which are the CD53 (CD53) and CD9 (CD9) markers, known to complex with integrins, and annexin I (ANXA1), credited with a potential anti-inflammatory activity, all of them performing important homeostatic roles by modulating innate immunity [34-36].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [34]
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- Authors
- D'Acquisto, F., Merghani, A., Lecona, E., Rosignoli, G., Raza, K., Buckley, C. D., Flower, R. J., & Perretti, M.
- Affiliations
- William Harvey Research Institute, Bart's and The London, Queen Mary School of Medicine and Dentistry, Charterhouse Square, London, United Kingdom;
- Queen Mary University of London (GB)
- University of Birmingham (GB)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-09-28
- Volume
- 109
- Issue
- 3
- Pages
- 1095-1102
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1855438
- OpenAlex
- W2088010225
- Cited by
- 195
- References
- 50
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 9 · 2023: 11 · 2022: 12 · 2021: 20 · 2020: 19 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 11 · 2012: 5
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust (040269, 069 234/Z/02/Z, 040 269/Z/96/A)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- annexin A1, T cell activation, T cell differentiation, Th1/Th2 skewing, T cell receptor signaling, NF-κB, NFAT, AP-1, collagen-induced arthritis, rheumatoid arthritis, CD4+ T cells, anti-inflammatory proteins, adaptive immunity
- MeSH terms
- CD69 Antigens, Animals, Antigens, Differentiation, T-Lymphocyte, Arthritis, Cell Differentiation, Cells, Cultured, Humans, Immunity, Lymphocyte Activation, Receptors, Antigen, T-Cell, T-Lymphocytes, Antigens, CD, Annexin A1, Th1 Cells, Lectins, C-Type, Cell Proliferation, Mice, Interleukin-2 Receptor alpha Subunit
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