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19 pages, 4475 KiB

Open AccessArticle

Trichinella spiralis Excretory–Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells

by Xi-Meng Sun, Kai Guo, Chun-Yue Hao, Bin Zhan, Jing-Jing Huang and Xinping Zhu

Cells 2019, 8(11), 1404; https://doi.org/10.3390/cells8111404 - 7 Nov 2019

Cited by 25 | Viewed by 3920

Abstract

Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory–secretory (ES) products, [...] Read more.

Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory–secretory (ES) products, characterized by increase of CD4⁺CD25⁺Foxp3⁺ and CD4⁺CD25⁻Foxp3⁺ Treg cells accompanied by high levels of IL-10 and TGF-β. T. spiralis adult worm excretory–secretory products (AES) and muscle larvae excretory–secretory products (MES) were both able to activate BMDCs in vitro to facilitate their maturation and to create regulatory cytokines IL-10 and TGF-β. The T. spiralis AES- and MES-pulsed dendritic cells (DCs) possessed abilities not only to present antigens to sensitized CD4⁺ T cell to stimulate their proliferation but also to induce naive CD4⁺ T cells to differentiate to Treg cells secreting IL-10 and TGF-β. The passive transfer of T. spiralis AES- and MES-pulsed bone marrow-derived dendritic cells (BMDCs) conferred the naive mice to acquire the differentiation of Treg cells. T. spiralis AES possesses a better ability to induce Treg cells than did MES, although the latter has the ability to induce CD4⁺CD25⁻Foxp3⁺ Treg cells. The results obtained in this study suggested that T. spiralis ES products stimulate the differentiation of host Treg cells possibly through activating dendritic cells to create a regulatory environment that benefits the survival of the parasite in the host. Full article

(This article belongs to the Special Issue Regulatory T (Treg) Cells in Health and Diseases)

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19 pages, 3017 KiB

Open AccessArticle

Hepatitis C Virus Improves Human Tregs Suppressive Function and Promotes Their Recruitment to the Liver

by Laurissa Ouaguia, Olivier Moralès, Lynda Aoudjehane, Czeslaw Wychowski, Abhishek Kumar, Jean Dubuisson, Yvon Calmus, Filomena Conti and Nadira Delhem

Cells 2019, 8(10), 1296; https://doi.org/10.3390/cells8101296 - 22 Oct 2019

Cited by 8 | Viewed by 3016

Abstract

Background: The role of regulatory T cells (Tregs) is now well established in the progression of hepatocellular carcinoma (HCC) linked to Hepatitis C virus (HCV) infection. However, nothing is known about the potential interplay between Tregs and HCV. In this pilot study, we [...] Read more.

Background: The role of regulatory T cells (Tregs) is now well established in the progression of hepatocellular carcinoma (HCC) linked to Hepatitis C virus (HCV) infection. However, nothing is known about the potential interplay between Tregs and HCV. In this pilot study, we have investigated the ability of Tregs to hang HCV on and the subsequent effect on their suppressive function and phenotype. Moreover, we have evaluated how HCV could promote the recruitment of Tregs by infected primary human hepatocytes. Methods: Tregs of healthy donors were incubated with JFH-1/HCVcc. Viral inoculation was assessed using adapted assays (RT-qPCR, Flow Citometry (FACS) and Western Blot (WB). Expression of Tregs phenotypic (CD4, CD25, CD127 and Foxp3) and functional (IL-10, GZMB, TGF-β1 and IL-2) markers was monitored by RT-qPCR, FACS and ELISA. Suppressive activity was validated by suppressive assays. Tregs recruitment by infected primary hepatic cells was evaluated using Boyden Chamber. Results: Tregs express the classical HCV receptors (CD81, CLDN1 and LDLR) and some co-receptors (CD5). HCV inoculation significantly increases the suppressive phenotype and activity of Tregs, and raises their anergy by inducing an unexpected IL-2 production. Moreover, HCV infection induces the expression of chemokines (CCL17, CXCL16, and CCL20) by primary hepatic human hepatocytes and chemokine receptors (CCR4, CXCR6 and CCR6) by Tregs. Finally, infected hepatocytes have a significantly higher potential to recruit Tregs in a seemingly CCL20-dependent manner. Conclusions: Direct interaction between HCV and Tregs represents a newly defined mechanism that could potentiate HCV immune evasion and favor intratumoral recruitment contributing to HCC progression. Full article

(This article belongs to the Special Issue Regulatory T (Treg) Cells in Health and Diseases)

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Review

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17 pages, 742 KiB

Open AccessReview

Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells

by Shin-ichi Koizumi and Hiroki Ishikawa

Cells 2019, 8(8), 939; https://doi.org/10.3390/cells8080939 - 20 Aug 2019

Cited by 43 | Viewed by 7417

Abstract

Foxp3-expressing regulatory T (Treg) cells can suppress the activity of various types of immune cells and play key roles in the maintenance of self-tolerance and in the regulation of immune responses against pathogens and tumor cells. Treg cells consist of heterogeneous subsets that [...] Read more.

Foxp3-expressing regulatory T (Treg) cells can suppress the activity of various types of immune cells and play key roles in the maintenance of self-tolerance and in the regulation of immune responses against pathogens and tumor cells. Treg cells consist of heterogeneous subsets that have distinct phenotypes and functions. Upon antigen stimulation, naïve-like thymus-derived Treg cells, which circulate in secondary lymphoid organs, can differentiate into effector Treg (eTreg) cells and migrate to and control immune homeostasis of peripheral tissues. eTreg cells are heterogeneous in terms of their ability to localize to specific tissues and suppress particular types of immune responses. Differentiation and function of diverse eTreg subsets are regulated by a variety of transcription factors that are activated by antigens and cytokines. In this article, we review the current understanding of the transcriptional regulation of differentiation and function of eTreg cells. Full article

(This article belongs to the Special Issue Regulatory T (Treg) Cells in Health and Diseases)

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