Complement Component C5a Promotes Expression of IL-22 and IL-17 from Human T Cells and Its Implication in Age-Related Macular Degeneration
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Background: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH), the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a) have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD. Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500. Results: We show that C5a promotes interleukin (IL)-22 and IL-17 expression by human CD4 + T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4 + cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls. Conclusions: Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.
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Elevated levels of effector T cell IL22 and IL17 cytokines were reported in AMD patients, suggesting an activation of cellular-mediated immunity.
“Elevated levels of effector T cell IL22 and IL17 cytokines were reported in AMD patients [64,65], suggesting an activation of cellular-mediated immunity.”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [64]
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The Immunological Basis of Degenerative Diseases of the Eye
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Animal models of age-related macular degeneration and their translatability into the clinic
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Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD)
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Ocular immune‐related diseases: molecular mechanisms and therapy
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Self-citationComplement Component C5a Permits the Coexistence of Pathogenic Th17 Cells and Type I IFN in Lupus
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- Authors
- Liu, B., Wei, L., Meyerle, C., Tuo, J., Sen, H. N., Li, Z., Chakrabarty, S., Agron, E., Chan, C.-C., Klein, M. L., Chew, E., Ferris, F., & Nussenblatt, R. B.
- Affiliations
- National Institutes of Health (US)
- Oregon Health & Science University (US)
- Corresponding author
- Nussenblatt, Robert B
- ORCID
- Venue
- Journal of Translational Medicine
- Published
- 2011-07-15
- Volume
- 9
- Issue
- 1
- Pages
- 1-12
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC3154861
- OpenAlex
- W2132154261
- Cited by
- 164
- References
- 44
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 10 · 2022: 11 · 2021: 8 · 2020: 9 · 2019: 4 · 2018: 8 · 2017: 8 · 2016: 14 · 2015: 16 · 2014: 22 · 2013: 20 · 2012: 9
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, IL-22, IL-17, CD4+ T cells, complement activation, complement factor H, B7, IL-1β, interleukin-6, T cell apoptosis, exudative AMD, inflammation
- MeSH terms
- Interleukin-22, Aged, Aged, 80 and over, Female, Humans, Interleukins, Macular Degeneration, Male, Middle Aged, Monocytes, T-Lymphocytes, Interleukin-6, Complement C5a, Apoptosis, Cytoprotection, Interleukin-17, Interleukin-1beta
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