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The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2

BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60–90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that coul...

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Autores principales: Espinar-Buitrago, M. S., Tarancon-Diez, L., Vazquez-Alejo, E., Magro-Lopez, E., Genebat, M., Romero-Candau, F., Leal, M., Muñoz-Fernandez, M. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320944/
https://www.ncbi.nlm.nih.gov/pubmed/37408063
http://dx.doi.org/10.1186/s12979-023-00351-x
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author Espinar-Buitrago, M. S.
Tarancon-Diez, L.
Vazquez-Alejo, E.
Magro-Lopez, E.
Genebat, M.
Romero-Candau, F.
Leal, M.
Muñoz-Fernandez, M. A.
author_facet Espinar-Buitrago, M. S.
Tarancon-Diez, L.
Vazquez-Alejo, E.
Magro-Lopez, E.
Genebat, M.
Romero-Candau, F.
Leal, M.
Muñoz-Fernandez, M. A.
author_sort Espinar-Buitrago, M. S.
collection PubMed
description BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60–90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. RESULTS: Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. CONCLUSION: The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. SUBJECTS: Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-023-00351-x.
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spelling pubmed-103209442023-07-06 The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2 Espinar-Buitrago, M. S. Tarancon-Diez, L. Vazquez-Alejo, E. Magro-Lopez, E. Genebat, M. Romero-Candau, F. Leal, M. Muñoz-Fernandez, M. A. Immun Ageing Research BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60–90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. RESULTS: Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. CONCLUSION: The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. SUBJECTS: Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-023-00351-x. BioMed Central 2023-07-05 /pmc/articles/PMC10320944/ /pubmed/37408063 http://dx.doi.org/10.1186/s12979-023-00351-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Espinar-Buitrago, M. S.
Tarancon-Diez, L.
Vazquez-Alejo, E.
Magro-Lopez, E.
Genebat, M.
Romero-Candau, F.
Leal, M.
Muñoz-Fernandez, M. A.
The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
title The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
title_full The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
title_fullStr The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
title_full_unstemmed The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
title_short The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
title_sort use of alpha 1 thymosin as an immunomodulator of the response against sars-cov2
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320944/
https://www.ncbi.nlm.nih.gov/pubmed/37408063
http://dx.doi.org/10.1186/s12979-023-00351-x
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