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Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature c...

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Autores principales: Fan, Xiaoli, Men, Ruoting, Huang, Chen, Shen, Mengyi, Wang, Tingting, Ghnewa, Yasmeen, Ma, Yun, Ye, Tinghong, Yang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957703/
https://www.ncbi.nlm.nih.gov/pubmed/31932577
http://dx.doi.org/10.1038/s41419-019-2217-6
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author Fan, Xiaoli
Men, Ruoting
Huang, Chen
Shen, Mengyi
Wang, Tingting
Ghnewa, Yasmeen
Ma, Yun
Ye, Tinghong
Yang, Li
author_facet Fan, Xiaoli
Men, Ruoting
Huang, Chen
Shen, Mengyi
Wang, Tingting
Ghnewa, Yasmeen
Ma, Yun
Ye, Tinghong
Yang, Li
author_sort Fan, Xiaoli
collection PubMed
description Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature cDCs increased in AIH patients and was positively correlated with disease severity. In experimental autoimmune hepatitis (EAH), hepatic accumulation of mature cDCs was observed, along with an increase in the periphery. Sequentially, bone marrow-derived dendritic cells (BMDC) from EAH mice exhibit more proinflammatory function than those from control mice. In vitro, ConA treatment promotes the maturation of BMDCs, which are characterized by higher expression of MHC-II, costimulatory molecules and cytokine secretion. ConA also induced the expression of autophagy-related protein and the formation of autophagosomes in DCs. To further investigate whether ConA-induced DC activation is associated with autophagy, we utilized 3-MA and bafilomycin A1 to block autophagy flux and accessed the maturation and function of DCs induced by ConA. 3-MA and bafilomycin A1 inhibited the mature status and proinflammatory cytokine secretion and diminished the proliferation and differentiation of CD4+ T cells when ConA-induced BMDCs cocultured CD4+ T cells. We demonstrated that cDCs contribute to the pathogenesis of AIH through excessive maturation. Aberrant autophagy flux plays a vital role in the immunogenic maturation of cDCs in AIH, and tolerogenic cDCs by inhibition of autophagy flux can be exploited as a new therapeutic approach for AIH.
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spelling pubmed-69577032020-01-14 Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation Fan, Xiaoli Men, Ruoting Huang, Chen Shen, Mengyi Wang, Tingting Ghnewa, Yasmeen Ma, Yun Ye, Tinghong Yang, Li Cell Death Dis Article Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature cDCs increased in AIH patients and was positively correlated with disease severity. In experimental autoimmune hepatitis (EAH), hepatic accumulation of mature cDCs was observed, along with an increase in the periphery. Sequentially, bone marrow-derived dendritic cells (BMDC) from EAH mice exhibit more proinflammatory function than those from control mice. In vitro, ConA treatment promotes the maturation of BMDCs, which are characterized by higher expression of MHC-II, costimulatory molecules and cytokine secretion. ConA also induced the expression of autophagy-related protein and the formation of autophagosomes in DCs. To further investigate whether ConA-induced DC activation is associated with autophagy, we utilized 3-MA and bafilomycin A1 to block autophagy flux and accessed the maturation and function of DCs induced by ConA. 3-MA and bafilomycin A1 inhibited the mature status and proinflammatory cytokine secretion and diminished the proliferation and differentiation of CD4+ T cells when ConA-induced BMDCs cocultured CD4+ T cells. We demonstrated that cDCs contribute to the pathogenesis of AIH through excessive maturation. Aberrant autophagy flux plays a vital role in the immunogenic maturation of cDCs in AIH, and tolerogenic cDCs by inhibition of autophagy flux can be exploited as a new therapeutic approach for AIH. Nature Publishing Group UK 2020-01-13 /pmc/articles/PMC6957703/ /pubmed/31932577 http://dx.doi.org/10.1038/s41419-019-2217-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fan, Xiaoli
Men, Ruoting
Huang, Chen
Shen, Mengyi
Wang, Tingting
Ghnewa, Yasmeen
Ma, Yun
Ye, Tinghong
Yang, Li
Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
title Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
title_full Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
title_fullStr Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
title_full_unstemmed Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
title_short Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
title_sort critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957703/
https://www.ncbi.nlm.nih.gov/pubmed/31932577
http://dx.doi.org/10.1038/s41419-019-2217-6
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