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Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis
Nocardia rubra cell-wall skeleton (Nr-CWS) is reported as an external immunotherapeutic enhancer with the advantage of antitumor effect on human cancers. However, the immune regulatory role of Nr-CWS is not fully illustrated. We studied mouse CD4(+) T lymphocytes isolated from mice spleen were induc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450467/ https://www.ncbi.nlm.nih.gov/pubmed/35473474 http://dx.doi.org/10.1177/00368504221092901 |
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author | Zhou, Meixiang Zhou, Shuping Han, Kun Zhang, Jie Chen, Qingyu Tian, Cong Zhu, Hongling Jiang, Mengyi Min, Daliu |
author_facet | Zhou, Meixiang Zhou, Shuping Han, Kun Zhang, Jie Chen, Qingyu Tian, Cong Zhu, Hongling Jiang, Mengyi Min, Daliu |
author_sort | Zhou, Meixiang |
collection | PubMed |
description | Nocardia rubra cell-wall skeleton (Nr-CWS) is reported as an external immunotherapeutic enhancer with the advantage of antitumor effect on human cancers. However, the immune regulatory role of Nr-CWS is not fully illustrated. We studied mouse CD4(+) T lymphocytes isolated from mice spleen were induced by Nr-CWS and observed that the differentiation of Th1 CD4(+) T cells and the cytokines of IL-2, TNF-α, IFN-γ were all enhanced by Nr-CWS. Furthermore, RNA sequencing was conducted to investigate the different mRNA profiling induced by Nr-CWS. We observed that paired box 8 (PAX8) was significantly up-regulated in Nr-CWS-treated Th1 cells compared to control. As a transcription factor, chromatin immunoprecipitation sequencing was carried out to study the genome-wide distribution of PAX8. Interestingly, we found that the binding domain of PAX8 was elevated by Nr-CWS, and the target genes associated with these binding sites showed a positive correlation between their transcription and PAX8 binding strength. Finally, we determined that Nr-CWS could enhance the activity of the PI3 K/Akt signaling pathway. Akt agonist could mimic the effect of Nr-CWS for PAX8 up-regulation, while Akt inhibitor compromised the expression of PAX8. Taken together, we determined a novel role of Nr-CWS in boosting the activity of Th1 maturation via the PI3 K/Akt/PAX8 axis. |
format | Online Article Text |
id | pubmed-10450467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-104504672023-08-26 Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis Zhou, Meixiang Zhou, Shuping Han, Kun Zhang, Jie Chen, Qingyu Tian, Cong Zhu, Hongling Jiang, Mengyi Min, Daliu Sci Prog Original Manuscript Nocardia rubra cell-wall skeleton (Nr-CWS) is reported as an external immunotherapeutic enhancer with the advantage of antitumor effect on human cancers. However, the immune regulatory role of Nr-CWS is not fully illustrated. We studied mouse CD4(+) T lymphocytes isolated from mice spleen were induced by Nr-CWS and observed that the differentiation of Th1 CD4(+) T cells and the cytokines of IL-2, TNF-α, IFN-γ were all enhanced by Nr-CWS. Furthermore, RNA sequencing was conducted to investigate the different mRNA profiling induced by Nr-CWS. We observed that paired box 8 (PAX8) was significantly up-regulated in Nr-CWS-treated Th1 cells compared to control. As a transcription factor, chromatin immunoprecipitation sequencing was carried out to study the genome-wide distribution of PAX8. Interestingly, we found that the binding domain of PAX8 was elevated by Nr-CWS, and the target genes associated with these binding sites showed a positive correlation between their transcription and PAX8 binding strength. Finally, we determined that Nr-CWS could enhance the activity of the PI3 K/Akt signaling pathway. Akt agonist could mimic the effect of Nr-CWS for PAX8 up-regulation, while Akt inhibitor compromised the expression of PAX8. Taken together, we determined a novel role of Nr-CWS in boosting the activity of Th1 maturation via the PI3 K/Akt/PAX8 axis. SAGE Publications 2022-04-27 /pmc/articles/PMC10450467/ /pubmed/35473474 http://dx.doi.org/10.1177/00368504221092901 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Manuscript Zhou, Meixiang Zhou, Shuping Han, Kun Zhang, Jie Chen, Qingyu Tian, Cong Zhu, Hongling Jiang, Mengyi Min, Daliu Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis |
title | Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis |
title_full | Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis |
title_fullStr | Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis |
title_full_unstemmed | Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis |
title_short | Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis |
title_sort | th1 immune maturation effects of nocardia rubra cell-wall skeleton via pi3k/akt/pax8 regulatory axis |
topic | Original Manuscript |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450467/ https://www.ncbi.nlm.nih.gov/pubmed/35473474 http://dx.doi.org/10.1177/00368504221092901 |
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