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. 2023 Nov;124(Pt A):110831.
doi: 10.1016/j.intimp.2023.110831. Epub 2023 Aug 24.

Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation

Abdul Wahid Ansari  1 , Fareed Ahmad  2 , Thesni Raheed  2 , Anh Jochebeth  2 , Jericha Miles Pamiloza Mateo  2 , Nabeel Abdulrahman  2 , Elizabeth Febu Joy  3 , Majid Ali Alam  2 , Joerg Buddenkotte  4 , Rifat Akram Hamoudi  5 , Martin Steinhoff  6
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Free article

Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation

Abdul Wahid Ansari et al. Int Immunopharmacol. 2023 Nov.
Free article

Abstract

The precise mechanism of macrolide antibiotic azithromycin (AZM) mediated CD4+ T cell suppression is not fully understood. Given the crucial role of co-stimulatory signaling in T-lymphocyte function, we tested in vitro effects of AZM on two of the most extensively investigated costimulatory molecules, ICOS and OX40 in context to CD4+ T cell proliferation. Using multi-color flow cytometry approach on TCR-activated healthy donor peripheral blood mononuclear cells, we observed a marked reduction in the frequencies and surface expression of ICOS and OX40 receptors following AZM treatment. Functionally, in contrast to ICOS- and OX40- CD3+ CD4+ T cells, AZM treated ICOS+ and OX40+ displayed profound reduction in cell proliferation. Furthermore, AZM treated T cells displaying reduced levels of ICOS and OX40 found to be associated with suppressed mTOR activity as detected by phosphorylation levels of S6 ribosomal protein. This study provides new insights on potential mechanism of AZM mediated inhibition of T cell proliferation by targeting costimulatory pathways.

Keywords: Azithromycin; ICOS; OX40; Proliferation; T cells; mTOR.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.