eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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1/2022
vol. 47
 
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abstract:
Experimental immunology

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

Xiaoxia Zhan
1
,
Xiaobing Jiang
1
,
Qiuying He
1
,
Liangyin Zhong
1
,
Yichong Wang
1
,
Yulan Huang
2
,
Shitong He
2
,
Junli Sheng
2
,
Jianwei Liao
3
,
Zhijie Zeng
1
,
Shengfeng Hu
2

  1. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  2. Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
  3. Cellular and Molecular Diagnostics Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
Cent Eur J Immunol 2022; 47 (1): 30-40
DOI: https://doi.org/10.5114/ceji.2022.113086
Online publish date: 2022/02/11
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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 Pam2CSK4. 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 Pam2CSK4 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.
keywords:

toll-like receptor 2 (TLR2), myeloid-derived suppressor cells (MDSCs), monocytic MDSCs (M-MDSCs), signal transducer and activator of transcription 3 (STAT3), inducible NO synthase (iNOS/NOS2), nitric oxide (NO), chronic inflammation
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