Pam2 lipopeptides enhance the immunosuppressive activity of monocytic myeloid-derived suppressor cells by STAT3 signal in chronic inflammation

Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR...

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Main Authors: Xiaoxia Zhan, Xiaobing Jiang, Qiuying He, Liangyin Zhong, Yichong Wang, Yulan Huang, Shitong He, Junli Sheng, Jianwei Liao, Zhijie Zeng, Shengfeng Hu
Format: Article
Language:English
Published: Termedia Publishing House 2022-02-01
Series:Central European Journal of Immunology
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Online Access:https://www.termedia.pl/Pam2-lipopeptides-enhance-the-immunosuppressive-activity-of-monocytic-myeloid-derived-suppressor-cells-by-STAT3-signal-in-chronic-inflammation,10,46311,1,1.html
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Summary:Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR2) has an important role in chronic inflammation and can be activated by a vast number and diversity of TLR2 ligands, for example Pam 2 CSK4. However, the regulatory effect of TLR2 signaling on MDSCs in chronic inflammation remains controversial. This study demonstrated that heat-killed Mycobacterium bovis BCG-induced pathology-free chronic inflammation triggered suppressive monocytic MDSCs (M-MDSCs) that expressed TLR2. Activation of TLR2 signaling by Pam 2 CSK4 treatment enhanced immunosuppression of M-MDSCs by upregulating inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production partly through signal transducer and activator of transcription 3 (STAT3) activation. Thus, TLR2 has a fundamental role in promoting the MDSC-mediated immunosuppressive environment during chronic inflammation and might represent a potentially therapeutic target in chronic inflammation disease.
ISSN:1426-3912
1644-4124