Evidence map›Paper›PMID 39211048›Full record

ArticleFrontiers in immunology2024

Azithromycin targets the CD27 pathway to modulate CD27hi T-lymphocyte expansion and type-1 effector phenotype.

Abdul Wahid Ansari, Manju Nidagodu Jayakumar, Fareed Ahmad, Thenmozhi Venkatachalam, Laila Salameh, Hema Unnikannan, Thesni Raheed, Abdul Khader Mohammed, Bassam Mahboub, Basel K Al-Ramadi and 3 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Abdul Wahid AnsariResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Manju Nidagodu JayakumarResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Fareed AhmadDermatology Institute, Interim Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Thenmozhi VenkatachalamResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Laila SalamehDepartment of Pulmonary Medicine, Rashid Hospital, Dubai, United Arab Emirates.
Hema UnnikannanResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Thesni RaheedDermatology Institute, Interim Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Abdul Khader MohammedResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Bassam MahboubDepartment of Pulmonary Medicine, Rashid Hospital, Dubai, United Arab Emirates.
Basel K Al-RamadiDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Qutayba HamidDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Martin SteinhoffDermatology Institute, Interim Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Rifat HamoudiResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Macrolide antibiotic azithromycin is widely used in clinical practice to treat respiratory tract infections and inflammatory diseases. However, its mechanism of action is not fully understood. Given the involvement of the CD27 pathway in the pathophysiology of various T-lymphocyte-mediated inflammatory, autoimmune, and lymphoproliferative diseases, we examined the impact of AZM on CD27 regulation and potential consequences on CD4+ and CD8+ T-cell phenotypes. Using cellular immunology approaches on healthy donors' peripheral blood mononuclear cells, we demonstrate AZM-mediated downregulation of surface CD27 expression as well as its extracellular release as soluble CD27. Notably, AZM-exposed CD27high (hi) cells were defective in their ability to expand compared to CD27intermediate (Int) and CD27low (lo) subsets. The defective CD27hi subset expansion was found to be associated with impaired cell proliferation and cell division. At the molecular level, the CD27hi subset exhibited lower mTOR activity than other subsets. Functionally, AZM treatment resulted in marked depletion of helper CD4+ (Th1) and cytotoxic CD8+ T-lymphocyte (Tc1)-associated CXCR3+CD27hi effector cells and inhibition of inflammatory cytokine IFN-γ production. These findings provide mechanistic insights on immunomodulatory features of AZM on T-lymphocyte by altering the CD27 pathway. From a clinical perspective, this study also sheds light on potential clinical benefits observed in patients on prophylactic AZM regimens against various respiratory diseases and opens avenues for future adjunct therapy against Th1- and Tc1-dominated inflammatory and autoimmune diseases.

Indexed as

AzithromycinSignal TransductionTumor Necrosis Factor Receptor Superfamily, Member 7Anti-Bacterial AgentsCD8-Positive T-LymphocytesCell ProliferationHumansLymphocyte ActivationPhenotypeTh1 CellsT-Lymphocyte SubsetsAnti-Bacterial AgentsAzithromycinTumor Necrosis Factor Receptor Superfamily, Member 7azithromycinCD27 subsetCXCR3inflammationmTORT-lymphocytestype-1 immunity

Identifiers

PMID39211048
PMCPMC11357905

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.