Interleukin-10 reorganizes the cytoskeleton of mature dendritic cells leading to their impaired biophysical properties and motilities.

Xiaoli Xu,Long Li,Zuquan Hu,Qinni Zheng,Jing Zhou,Zhu Zeng,Yun Wang,Jinhua Long,Yi Jia,Weijuan Yao,Wei Qiu,Chunlin Zhang,Xianmei Liu,Yuntao Wu

doi:10.1371/journal.pone.0172523

Abstract

Interlukin-10 (IL-10) is an immunomodulatory cytokine which predominantly induces immune-tolerance. It has been also identified as a major cytokine in the tumor microenvironment that markedly mediates tumor immune escape. Previous studies on the roles of IL-10 in tumor immunosuppression mainly focus on its biochemical effects. But the effects of IL-10 on the biophysical characteristics of immune cells are ill-defined. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a key role in the anti-tumor immune response. IL-10 can affect the immune regulatory functions of DCs in various ways. In this study, we aim to explore the effects of IL-10 on the biophysical functions of mature DCs (mDCs). mDCs were treated with different concentrations of IL-10 and their biophysical characteristics were identified. The results showed that the biophysical properties of mDCs, including electrophoresis mobility, osmotic fragility and deformability, as well as their motilities, were impaired by IL-10. Meanwhile, the cytoskeleton (F-actin) of mDCs was reorganized by IL-10. IL-10 caused the alternations in the expressions of fasin1 and profilin1 as well as the phosphorylation of cofilin1 in a concentration-dependent fashion. Moreover, Fourier transformed infrared resonance data showed that IL-10 made the status of gene transcription and metabolic turnover of mDCs more active. These results demonstrate a new aspect of IL-10’s actions on the immune system and represent one of the mechanisms for immune escape of tumors. It may provide a valuable clue to optimize and improve the efficiency of DC-based immunotherapy against cancer.

Highlights

Interleukin-10 (IL-10) is an immunomodulatory cytokine which is produced by a variety of cells, such as regulatory T lymphocytes subsets, monocytes, activated macrophages and other cells [1]
Our results showed that the cytoskeleton (F-actin) of mature DCs (mDCs) was reorganized by IL10, resulting in their impaired biophysical characteristics and motilities, which were associated with the altered expression levels of some cytoskeleton-binding proteins
We investigated the effects of IL-10 on the biophysical characteristics of mDCs, including the deformability, osmotic fragility and electrophoresis mobility

Summary

Introduction

Interleukin-10 (IL-10) is an immunomodulatory cytokine which is produced by a variety of cells, such as regulatory T lymphocytes subsets, monocytes, activated macrophages and other cells [1]. It exists in the tumor microenvironments, especially for advanced tumors [6]. IL-10 mediates tumor immunosuppression and leads to the negative prognosis of tumor-bearing hosts [7,8], whose underlying mechanisms are that IL-10 could inhibit T cell proliferation and induce T cell to differentiate to the regulatory T cell phenotype [9]. Current evidences show that B cells expressing IL-10 could suppress the activities of cytotoxic CD4+ T cells in hepatocellular carcinoma, leading to the poor prognosis [12]. These studies indicate that IL-10 acts as a detrimental member in the tumor microenvironment. The effects of IL-10 on the biophysical characteristics of immune cells are still elusive

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