ArticlePLoS pathogens2013
Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- The Hitchhiker Guide to CD4Frontiers in immunology · 2021Pooled it
- Identification of novel HIV-1 dependency factors in primary CCR4(+)CCR6(+)Th17 cells via a genome-wide transcriptional approach.Retrovirology · 2015Pooled it
- IL-21 and anti-α4β7 dual therapy during ART promotes immunological and microbiome responses in SIV-infected macaques.JCI insight · 2025Article
- Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.Nature immunology · 2024Article
- IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.Aging cell · 2023Article
- Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161Viruses · 2023Article
- Intricacies of TGF-β signaling in Treg and Th17 cell biology.Cellular & molecular immunology · 2023Review
- Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19-A Swedish Cohort Study.Biomedicines · 2023Article
- Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy.The Journal of clinical investigation · 2022Article
- IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells.iScience · 2021Article
- IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection.JCI insight · 2021Article
- Interleukin-21 in Viral Infections.International journal of molecular sciences · 2021Review
- Review
- IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques.Nature communications · 2021Article
- Role of NKG2a/ciScience · 2021Article
- Effects of therapeutic vaccination on the control of SIV in rhesus macaques with variable responsiveness to antiretroviral drugs.PloS one · 2021Article
- Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques.Journal of virology · 2020Article
- CTLA-4 and PD-1 dual blockade induces SIV reactivation without control of rebound after antiretroviral therapy interruption.Nature medicine · 2020Article
- Pharmacological Inhibition of PPARy Boosts HIV Reactivation and Th17 Effector Functions, While Preventing Progeny Virion Release and dePathogens & immunity · 2020Article
- Safety and Immunological Evaluation of Interleukin-21 Plus Anti-α4β7 mAb Combination Therapy in Rhesus Macaques.Frontiers in immunology · 2020Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs), preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239) and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i) higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii) higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.