Cited by 96Erythropoietin and Anemia TreatmentCell death mechanisms and regulationCytokine Signaling Pathways and Interactions

Multiple members of the TNF superfamily contribute to IFN-γ-mediated inhibition of erythropoiesis

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Felli, Nadia, Pedini, Francesca, Zeuner, Ann, Petrucci, Eleonora, Testa, Ugo, Conticello, Concetta, Biffoni, Mauro, Di Cataldo, Andrea +3 more·2005·The Journal of Immunology

Abstract

IFN-γ inhibits the growth and differentiation of erythroid precursor cells and mediates hemopoietic suppression through mechanisms that are not completely understood. We found that treatment of human erythroid precursor cells with IFN-γ up-regulates the expression of multiple members of the TNF family, including TRAIL and the recently characterized protein TWEAK. TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) were expressed by purified erythroblasts at all the stages of maturation. Exposure to recombinant TWEAK or agonist anti-Fn14 Abs was able to inhibit erythroid cell growth and differentiation through caspase activation. Because other members of the TNF family such as TRAIL and CD95 ligand (CD95L) are known to interfere with erythroblast growth and differentiation, we investigated the role of different TNF/TNFR family proteins as potential effectors of IFN-γ in the immature hemopoietic compartment. Treatment of erythroid precursor cells with agents that blocked either TRAIL, CD95L, or TWEAK activity was partially able to revert the effect of IFN-γ on erythroid proliferation and differentiation. However, the simultaneous inhibition of TRAIL, TWEAK, and CD95L resulted in a complete abrogation of IFN-γ inhibitory effects, indicating the requirement of different receptor-mediated signals in IFN-γ-mediated hemopoietic suppression. These results establish a new role for TWEAK and its receptor in normal and IFN-γ-mediated regulation of hematopoiesis and show that the effects of IFN-γ on immature erythroid cells depend on multiple interactions between TNF family members and their receptors.

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Crossref · 10.4049/jimmunol.175.3.1464

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  • TNF-a induces activation of caspases in erythroid precursor cells; subsequent cleavage and depletion of GATA-1 boosts PU.1-mediated skewing.

    “In concert, another prominent inflammatory cytokine, TNF-a, induces activation of caspases in erythroid precursor cells.The subsequent cleavage and depletion of GATA-1 as vital transcription factor for the erythroid lineage boosts the PU.1-mediated skewing.29,30”

    From Inflammatory bone marrow microenvironment (2019) · cites this paper as [30]

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Authors
Felli, N., Pedini, F., Zeuner, A., Petrucci, E., Testa, U., Conticello, C., Biffoni, M., Di Cataldo, A., Winkles, J. A., Peschle, C., & De Maria, R.
Affiliations
  • Istituto Superiore di Sanità (IT)
  • IOM Foundation , Catania ,
  • Pediatric Hematology and Oncology Unit, University of Catania ,
  • University of Maryland, Baltimore (US)
  • Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità , Rome ,
Venue
The Journal of Immunology
Published
2005-08-01
Volume
175
Issue
3
Pages
1464-1472
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1503710233
Cited by
96
References
47
Citations by year
2026: 3 · 2025: 4 · 2024: 1 · 2022: 5 · 2021: 2 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 8 · 2012: 2
FWCI
3.54
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Associazione Italiana per la Ricerca sul Cancro
  • National Institutes of Health (HL-39727)
  • National Heart, Lung, and Blood Institute (HL-39727)
Topics
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interferon-gamma, erythropoiesis, TNF superfamily, TWEAK, Fn14, TRAIL, Fas ligand, erythroid precursors, erythroblast differentiation, caspase activation, hematopoietic suppression, TNF receptor signaling
MeSH terms
Cytokine TWEAK, TWEAK Receptor, Carrier Proteins, Cell Differentiation, Cells, Cultured, Erythroblasts, Erythropoiesis, Growth Inhibitors, Humans, Immunologic Factors, Interferon-gamma, Ligands, Membrane Glycoproteins, Membrane Proteins, Tumor Necrosis Factor-alpha, Up-Regulation, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factors, Cell Proliferation, Apoptosis Regulatory Proteins, TNF-Related Apoptosis-Inducing Ligand, Fas Ligand Protein

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