Open Access

ARTICLE

Transforming Growth Factor-β₁ Remodels the Cytoskeleton Organization of Mature Dendritic Cells via Smad2/3 Signaling Pathway

Hui Yang^{1, §}, Jinhua Long^1,2,3,§, Yun Wang^1,3, Wenhui Hu¹, Zuquan Hu^1,2, Jin Zhou^1,2, Lina Liu^1,2, Wei Qiu^1,2, Fuzhou Tang^1,2, Weijuan Yao⁴, Long Li^{5, 6, *}, Zhu Zeng^{1, 2, 6, 7, *}

1 Immune Cells and Antibody Engineering Research Center of Guizhou Province/Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550004, P.R. China .
2 School of Biology and Engineering, Guizhou Medical University, Guiyang 550004, P.R. China.
3 Department of Head and Neck, Affiliated Cancer Hospital, Guizhou Medical University, Guiyang 550004, P.R. China.
4 Hemorheology Center, School of Basic Medical Sciences, Health Science Center of Peking University, Beijing 100191, P.R. China.
5 Department of Nephrology, The Third Affiliated Hospital of Guizhou Medical University, Duyun 558000, Guizhou Province, P. R. China.
6 Key Laboratory of Environmental Pollution and Disease Surveillance and Control of Ministry of Education, Guiyang 550025, P. R. China.
* Corresponding Authors: Zhu Zeng. Email: zengzhu100@sina.com;
Long Li. Email: gzyxyll@medmail.com.cn.
§ These authors are equal contribution.

Molecular & Cellular Biomechanics 2018, 15(1), 21-36. https://doi.org/10.3970/mcb.2018.015.021

Abstract

Dendritic cells (DCs) are the most potent professional antigen presenting cells as now known, which play critical roles in the initiation, programming and regulation of the immune response. Transforming growth factor-β₁ (TGF-β₁), one of the major suppressive cytokines in tumor microenvironment, can deteriorate the biomechanical characteristics and motility of mature dendritic cells (mDCs)，but the underlying molecular mechanisms are not well defined. In this study, the effects of TGF-β₁ on the motilities and T cell priming capabilities of mDCs as well as the molecular regulatory mechanisms were investigated. The results showed that the cytoskeleton (F-actin) organizations of mDCs were abnormally remodeled by TGF-β₁. Simultaneously, the migration and immune priming capabilities of mDCs were impaired by TGF-β₁ via Smad2/3 signaling pathway. It’s significant for further understanding the interaction of DCs and TGF-β₁ in tumor host, as well as the immune escape mechanism of cancer, which may be important for enhancing the clinical efficiency of DCs-based immunotherapy against cancer.

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Keywords

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