Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells
Abstract
Heavy chain ferritin (H-ferritin) is a component of the iron-binding protein, ferritin. We have previously shown that H-ferritin inhibits anti-CD3-stimulated lymphocyte proliferation and that this was due to increased production of interleukin-10 (IL-10). In the present study we have shown that induction of IL-10 production was due to effects of H-ferritin on adherent antigen-presenting cells (APCs) in blood and monocyte-derived dendritic cells (MoDCs). IL-10 was produced by a subpopulation of CD4 T cells, which expressed the CD25 component of the IL-2 receptor and the CTLA-4 receptor characteristic of regulatory T cells. The changes induced in MoDCs were compared with those induced by CD40L and their significance tested by inhibition with monoclonal antibodies. These studies indicated that H-ferritin induced relatively greater expression of CD86 and B7-H1 on MoDCs and that monoclonal antibodies against their receptors, CTLA-4 and programmed death receptor-1 (PD-1), inhibited IL-10 production from the regulatory T cells. H-ferritin did not appear to induce direct production of the cytokines IL-2, IL-4, IL-6, IL-10, IL-12, or interferon-gamma from the DCs. These results are consistent with the thesis that H-ferritin induces B7-H1 and CD86 (B7-2) on APCs, which in turn induce IL-10 production from regulatory T cells. This is possibly one mechanism by which melanoma cells may induce changes in APCs in the vicinity of the tumor and result in suppression of immune responses by induction of regulatory T cells.
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FTH is secreted by melanoma cells and circulates in plasma.
“FTH is secreted by melanoma cells and circulates in the plasma.”
From Iron in infection and immunity (2020) · cites this paper as Gray et al., 2002
FTH acts on antigen-presenting cells and induces expression of CD86 and B7-H1.
“FTH then acts on antigen-presenting cells (APC) and induces the expression of CD86 and B7-H1 (Gray et al., 2002(Gray et al., , 2003)).”
From Iron in infection and immunity (2020) · cites this paper as Gray et al., 2002
Iron present in FTH affects the function of Tregs, as demonstrated in malignant melanoma patients.
“Indirectly, iron present in FTH affects the function of T regs as demonstrated in malignant melanoma patients.”
From Iron in infection and immunity (2020) · cites this paper as Gray et al., 2002
Iron binding and release by Tf are coordinated by a conformational change in which the two subdomains of each lobe open, and the N1, N2, C1, and C2 domains twist.
“Iron binding and release are coordinated by a conformational change in which the two subdomains of each lobe open, and the N1, N2, C1, and C2 domains twist (114, 115).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [114]
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- Authors
- Gray, C. P., Arosio, P., & Hersey, P.
- Affiliations
- University of Brescia (IT)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2002-05-01
- Volume
- 99
- Issue
- 9
- Pages
- 3326-3334
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2012723575
- Cited by
- 118
- References
- 60
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 2 · 2021: 2 · 2020: 10 · 2019: 6 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2012: 5
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- heavy chain ferritin, regulatory T cells, dendritic cells, monocyte-derived dendritic cells, IL-10, antigen-presenting cells, CD86, PD-L1, CTLA-4, PD-1, CD25, CD40 ligand, melanoma, immunosuppression, iron-binding proteins
- MeSH terms
- Cell Communication, Cell Differentiation, Dendritic Cells, Ferritins, Humans, Lymphocyte Activation, T-Lymphocytes, Receptors, Interleukin-2, CD4-Positive T-Lymphocytes, Cytokines, Interleukin-10, CD40 Ligand
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