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Int J Biol Sci 2022; 18(4):1580-1593. doi:10.7150/ijbs.68865 This issue Cite

Research Paper

Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis

Lijun Dong1,2#, Honglian Jiang2,3#, Kai Chen3, Jingwen Xie2,3, Qing An4, Fan Deng2,3, Zhengyang Sun1, Yunzhi Liu2,3, Jia Zhou3, Liyun Zhang3, Xiao Lu3, Mingyong Wang5, Zhengliang Chen3,6✉, Xiaoming Zou1✉, Daming Zuo1,2,7✉

1. The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510900, China
2. Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, China
3. Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China
4. State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China
5. School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China
6. Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, Guangdong 510515, China
7. Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
# These authors have contributed equally to this work.

✉ Corresponding authors: Zhengliang Chen, Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China. Tel: 86-20-61648477; Fax: 86-20-61648221; Email: zhlchenedu.cn. Xiaoming Zou, T More

Citation:
Dong L, Jiang H, Chen K, Xie J, An Q, Deng F, Sun Z, Liu Y, Zhou J, Zhang L, Lu X, Wang M, Chen Z, Zou X, Zuo D. Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis. Int J Biol Sci 2022; 18(4):1580-1593. doi:10.7150/ijbs.68865. https://www.ijbs.com/v18p1580.htm
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Abstract

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Background: Mannan-binding lectin (MBL), a soluble pattern recognition molecule in the innate immune system, is reported to be associated with the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are mainly characterized by immunosuppressive activities involving several inflammatory diseases such as cancer, infection, and arthritis. Some of the factors inducing their apoptosis are known, however, mechanisms have not been identified. The underlying impact of MBL on the MDSCs especially under inflammatory conditions remains unknown. This study was designed to investigate whether MBL affects MDSCs survival during inflammation conditions.

Methods: WT and MBL-deficient (MBL-/-) mice were induced on day 0 of the experiment by subcutaneous injection of complete Freund's adjuvant and then injected with incomplete Freund's adjuvant into the knee joint space under general anesthesia on day 14 to induce inflammatory arthritis. The proportions of MDSCs in the spleen and blood and the serum level of the inflammatory cytokines were measured. In vitro study, MDSCs were isolated from the bone marrow of WT and MBL-/- mice and cultured in the presence of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 5 days with or without tumor necrosis factor-alpha (TNF-α).

Results: After adjuvant treatment, MBL-/- mice had a significantly lower frequency of MDSCs as well as elevated serum inflammatory cytokines levels compared to WT mice. MBL deficiency markedly inhibited the MDSCs frequency from mice bone marrow induced by IL-6 and GM-CSF in the presence of TNF-α in vitro. Mechanistic studies established that MBL inhibited MDSCs apoptosis via down-regulation of TNF-α/tumor necrosis factor-alpha receptor 1 (TNFR1) signaling pathway and subsequent caspase 3-dependent manner.

Conclusion: Mannan-binding lectin deficiency inhibits myeloid-derived suppressor cells expansion via modulating TNF-α triggered apoptosis.

Keywords: mannan-binding lectin, myeloid-derived suppressor cells, tumor necrosis factor-α, apoptosis

Citation styles

APA
Dong, L., Jiang, H., Chen, K., Xie, J., An, Q., Deng, F., Sun, Z., Liu, Y., Zhou, J., Zhang, L., Lu, X., Wang, M., Chen, Z., Zou, X., Zuo, D. (2022). Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis. International Journal of Biological Sciences, 18(4), 1580-1593. https://doi.org/10.7150/ijbs.68865.

ACS
Dong, L.; Jiang, H.; Chen, K.; Xie, J.; An, Q.; Deng, F.; Sun, Z.; Liu, Y.; Zhou, J.; Zhang, L.; Lu, X.; Wang, M.; Chen, Z.; Zou, X.; Zuo, D. Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis. Int. J. Biol. Sci. 2022, 18 (4), 1580-1593. DOI: 10.7150/ijbs.68865.

NLM
Dong L, Jiang H, Chen K, Xie J, An Q, Deng F, Sun Z, Liu Y, Zhou J, Zhang L, Lu X, Wang M, Chen Z, Zou X, Zuo D. Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis. Int J Biol Sci 2022; 18(4):1580-1593. doi:10.7150/ijbs.68865. https://www.ijbs.com/v18p1580.htm

CSE
Dong L, Jiang H, Chen K, Xie J, An Q, Deng F, Sun Z, Liu Y, Zhou J, Zhang L, Lu X, Wang M, Chen Z, Zou X, Zuo D. 2022. Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis. Int J Biol Sci. 18(4):1580-1593.

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