Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice

As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DC...

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Main Authors: Feifei Huo, Dongbei Li, Bo Zhao, Yadong Luo, Bingjie Zhao, Xueyang Zou, Yi Li, Wei Yang
Format: Article
Language:English
Published: Taylor & Francis Group 2018-01-01
Series:Autoimmunity
Subjects:
Online Access:http://dx.doi.org/10.1080/08916934.2017.1422124
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author Feifei Huo
Dongbei Li
Bo Zhao
Yadong Luo
Bingjie Zhao
Xueyang Zou
Yi Li
Wei Yang
author_facet Feifei Huo
Dongbei Li
Bo Zhao
Yadong Luo
Bingjie Zhao
Xueyang Zou
Yi Li
Wei Yang
author_sort Feifei Huo
collection DOAJ
description As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis. To determine the role of Aire in maintaining immune tolerance by bone marrow-derived dendritic cells (BMDCs), in the present study we utilized Aire-knockout mice to examine the changes of maturation status and TRAs expression on BMDCs, additionally investigate the differentiation of CD4+ T cells. The results showed that expression of costimulatory molecule and major histocompatibility complex class II (MHC-II) molecule was increased and expression of various TRAs was decreased in BMDCs from Aire-knockout mice. Aire deficiency reduced the differentiation of naïve CD4+ T cells into type 2T helper (Th2) cells and regulatory T cells (Tregs) but enhanced the differentiation of naïve CD4+ T cells into Th1 cells, Th17 cells, and follicular helper T (Tfh) cells. The results demonstrate that Aire expressed by BMDCs plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.
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spelling doaj.art-627d507f34be4f12ba50abbb4105d0492023-09-15T10:01:07ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2018-01-01511101710.1080/08916934.2017.14221241422124Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in miceFeifei Huo0Dongbei Li1Bo Zhao2Yadong Luo3Bingjie Zhao4Xueyang Zou5Yi Li6Wei Yang7Jilin UniversityXinxiang Medical UniversityJilin UniversityJilin UniversityJilin UniversityJilin UniversityJilin UniversityJilin UniversityAs a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis. To determine the role of Aire in maintaining immune tolerance by bone marrow-derived dendritic cells (BMDCs), in the present study we utilized Aire-knockout mice to examine the changes of maturation status and TRAs expression on BMDCs, additionally investigate the differentiation of CD4+ T cells. The results showed that expression of costimulatory molecule and major histocompatibility complex class II (MHC-II) molecule was increased and expression of various TRAs was decreased in BMDCs from Aire-knockout mice. Aire deficiency reduced the differentiation of naïve CD4+ T cells into type 2T helper (Th2) cells and regulatory T cells (Tregs) but enhanced the differentiation of naïve CD4+ T cells into Th1 cells, Th17 cells, and follicular helper T (Tfh) cells. The results demonstrate that Aire expressed by BMDCs plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.http://dx.doi.org/10.1080/08916934.2017.1422124autoimmune regulatordendritic cellsimmune tolerancetissue-restricted antigenscd4+ t cell
spellingShingle Feifei Huo
Dongbei Li
Bo Zhao
Yadong Luo
Bingjie Zhao
Xueyang Zou
Yi Li
Wei Yang
Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice
Autoimmunity
autoimmune regulator
dendritic cells
immune tolerance
tissue-restricted antigens
cd4+ t cell
title Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice
title_full Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice
title_fullStr Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice
title_full_unstemmed Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice
title_short Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice
title_sort deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow derived dendritic cells in mice
topic autoimmune regulator
dendritic cells
immune tolerance
tissue-restricted antigens
cd4+ t cell
url http://dx.doi.org/10.1080/08916934.2017.1422124
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