Ansari, Abdul Wahid;
Jayakumar, Manju Nidagodu;
Ahmad, Fareed;
Venkatachalam, Thenmozhi;
Salameh, Laila;
Unnikannan, Hema;
Raheed, Thesni;
... Hamoudi, Rifat; + view all
(2024)
Azithromycin targets the CD27 pathway to modulate CD27hi T-lymphocyte expansion and type-1 effector phenotype.
Frontiers in Immunology
, 15
, Article 1447625. 10.3389/fimmu.2024.1447625.
Preview |
Text
Azithromycin targets the CD27 pathway to modulate CD27hi T-lymphocyte expansion and type-1 effector phenotype.pdf - Published Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Azithromycin targets the CD27 pathway to modulate CD27hi T-lymphocyte expansion and type-1 effector phenotype |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2024.1447625 |
| Publisher version: | https://doi.org/10.3389/fimmu.2024.1447625 |
| Language: | English |
| Additional information: | © 2024 Ansari, Jayakumar, Ahmad, Venkatachalam, Salameh, Unnikannan, Raheed, Mohammed, Mahboub, Al-Ramadi, Hamid, Steinhoff and Hamoudi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | azithromycin, CD27 subset, T-lymphocytes, inflammation, mTOR, type-1 immunity, CXCR3 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10205475 |
Archive Staff Only
 |
View Item |
