Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation
<p dir="ltr">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 invest...
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2023
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| _version_ | 1864513552586375168 |
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| author | Abdul Wahid Ansari (9442697) |
| author2 | Fareed Ahmad (134672) Thesni Raheed (17017779) Anh Jochebeth (17017782) Jericha Miles Pamiloza Mateo (17017785) Nabeel Abdulrahman (725914) Elizabeth Febu Joy (17017788) Majid Ali Alam (17017791) Joerg Buddenkotte (6293584) Rifat Akram Hamoudi (9442709) Martin Steinhoff (5340194) |
| author2_role | author author author author author author author author author author |
| author_facet | Abdul Wahid Ansari (9442697) Fareed Ahmad (134672) Thesni Raheed (17017779) Anh Jochebeth (17017782) Jericha Miles Pamiloza Mateo (17017785) Nabeel Abdulrahman (725914) Elizabeth Febu Joy (17017788) Majid Ali Alam (17017791) Joerg Buddenkotte (6293584) Rifat Akram Hamoudi (9442709) Martin Steinhoff (5340194) |
| author_role | author |
| dc.creator.none.fl_str_mv | Abdul Wahid Ansari (9442697) Fareed Ahmad (134672) Thesni Raheed (17017779) Anh Jochebeth (17017782) Jericha Miles Pamiloza Mateo (17017785) Nabeel Abdulrahman (725914) Elizabeth Febu Joy (17017788) Majid Ali Alam (17017791) Joerg Buddenkotte (6293584) Rifat Akram Hamoudi (9442709) Martin Steinhoff (5340194) |
| dc.date.none.fl_str_mv | 2023-11-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.intimp.2023.110831 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Azithromycin_downregulates_ICOS_CD278_and_OX40_CD134_expression_and_mTOR_activity_of_TCR-activated_T_cells_to_inhibit_proliferation/24173190 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Pharmacology and pharmaceutical sciences Azithromycin T cells ICOS OX40 Proliferation mTOR |
| dc.title.none.fl_str_mv | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: International Immunopharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.intimp.2023.110831" target="_blank">https://dx.doi.org/10.1016/j.intimp.2023.110831</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_57ee0aeb84cb7ae4d90d5f4dc21d68a7 |
| identifier_str_mv | 10.1016/j.intimp.2023.110831 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24173190 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferationAbdul Wahid Ansari (9442697)Fareed Ahmad (134672)Thesni Raheed (17017779)Anh Jochebeth (17017782)Jericha Miles Pamiloza Mateo (17017785)Nabeel Abdulrahman (725914)Elizabeth Febu Joy (17017788)Majid Ali Alam (17017791)Joerg Buddenkotte (6293584)Rifat Akram Hamoudi (9442709)Martin Steinhoff (5340194)Biomedical and clinical sciencesImmunologyPharmacology and pharmaceutical sciencesAzithromycinT cellsICOSOX40ProliferationmTOR<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: International Immunopharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.intimp.2023.110831" target="_blank">https://dx.doi.org/10.1016/j.intimp.2023.110831</a></p>2023-11-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.intimp.2023.110831https://figshare.com/articles/journal_contribution/Azithromycin_downregulates_ICOS_CD278_and_OX40_CD134_expression_and_mTOR_activity_of_TCR-activated_T_cells_to_inhibit_proliferation/24173190CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/241731902023-11-01T00:00:00Z |
| spellingShingle | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation Abdul Wahid Ansari (9442697) Biomedical and clinical sciences Immunology Pharmacology and pharmaceutical sciences Azithromycin T cells ICOS OX40 Proliferation mTOR |
| status_str | publishedVersion |
| title | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| title_full | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| title_fullStr | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| title_full_unstemmed | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| title_short | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| title_sort | Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation |
| topic | Biomedical and clinical sciences Immunology Pharmacology and pharmaceutical sciences Azithromycin T cells ICOS OX40 Proliferation mTOR |