Abstract |
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.
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Authors | Meixiang Zhou, Shuping Zhou, Kun Han, Jie Zhang, Qingyu Chen, Cong Tian, Hongling Zhu, Mengyi Jiang, Daliu Min |
Journal | Science progress
(Sci Prog)
2022 Apr-Jun
Vol. 105
Issue 2
Pg. 368504221092901
ISSN: 2047-7163 [Electronic] England |
PMID | 35473474
(Publication Type: Journal Article)
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Chemical References |
- Cell Wall Skeleton
- cell wall skeleton, Nocardia
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Cell Wall Skeleton
(pharmacology)
- Mice
- Phosphatidylinositol 3-Kinases
(genetics, metabolism)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- Rhodococcus
- Signal Transduction
(drug effects)
- Th1 Cells
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