ArticlePLoS pathogens2018
Neddylation contributes to CD4+ T cell-mediated protective immunity against blood-stage Plasmodium infection.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- The LEF1-LAG3 axis regulates CD4Parasites & vectors · 2026Article
- [Endogenous neddylation in B cells regulates immune responses in mice].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis.Clinical science (London, England : 1979) · 2025Article
- CD3Frontiers in immunology · 2025Review
- Genomic regions associated with bovine respiratory disease in pacific northwest Holstein cattle.Frontiers in veterinary science · 2025Article
- Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer.Nature communications · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis.Signal transduction and targeted therapy · 2024Article
- Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.Biomarker research · 2024Review
- Authentication and validation of key genes in the treatment of atopic dermatitis with Runfuzhiyang powder: combined RNA-seq, bioinformatics analysis, and experimental research.Frontiers in genetics · 2024Article
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia.Leukemia · 2023Article
- Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration.American journal of human genetics · 2023Article
- Neddylation Regulation of Immune Responses.Research (Washington, D.C.) · 2023Review
- Review
- Recycling and Reshaping-E3 Ligases and DUBs in the Initiation of T Cell Receptor-Mediated Signaling and Response.International journal of molecular sciences · 2022Review
- Association Between Neddylation and Immune Response.Frontiers in cell and developmental biology · 2022Review
- Neddylation and anti-tumor immunity.Oncotarget · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4+ T cells play predominant roles in protective immunity against blood-stage Plasmodium infection, both for IFN-γ-dependent effector mechanisms and providing B cell helper signals. Neddylation, an ubiquitination-like process triggered by covalent conjugation of NEDD8 to specific targets, has emerged as a potential regulator of T cell activities to TCR engagement. However, its contribution to T cell-mediated immunity to blood-stage malaria remains unclear. Here using an experimental model induced by Plasmodium yoelii 17XNL, and conditional knockout mice with T cell-specific deficiency of crucial components of neddylation pathway, we demonstrate activation of neddylation in T cells during blood-stage Plasmodium infection is essential for parasite control and host survival. Mechanistically, we show that apart from promoting CD4+ T cell activation, proliferation, and development of protective T helper 1 (Th1) cell response as suggested previously, neddylation is also required for supporting CD4+ T cell survival, mainly through B-cell lymphoma-2 (Bcl-2) mediated suppression of the mitochondria-dependent apoptosis. Furthermore, we provide evidence that neddylation contributes to follicular helper T (Tfh) cell differentiation, probably via augmenting the ubiquitin ligase Itch activity and proteasomal degradation of FoxO1, thereby facilitating germinal center (GC) formation and parasite-specific antibody production. This study identifies neddylation as a positive regulator of anti-Plasmodium immunity and provides insight into an involvement of such pathway in host resistance to infectious diseases.
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