Cargando…
RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism
Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and under...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692153/ https://www.ncbi.nlm.nih.gov/pubmed/34975327 http://dx.doi.org/10.7150/ijbs.65402 |
_version_ | 1784618898122866688 |
---|---|
author | Liu, Man Zhang, Hongxia Zhang, Lu Liu, Xin Zhou, Simin Wang, Xiaoyi Zhong, Weilong Zhang, Jie Wang, Bangmao Zhao, Jingwen Zhou, Lu |
author_facet | Liu, Man Zhang, Hongxia Zhang, Lu Liu, Xin Zhou, Simin Wang, Xiaoyi Zhong, Weilong Zhang, Jie Wang, Bangmao Zhao, Jingwen Zhou, Lu |
author_sort | Liu, Man |
collection | PubMed |
description | Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and underlying mechanism in AIH are poorly understood. Here, we detected the increased expression and activation of RIP3 in livers of patients and animal models with AIH. The inhibition of RIP3 kinase by GSK872 prevented concanavalin A (ConA)-induced immune-mediated hepatitis (IMH) by reduced hepatic proinflammatory cytokines and immune cells including Th17 cells and macrophages. Further experiments revealed that RIP3 inhibition resulted in an increase in CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) with immunoregulatory properties in the liver, spleen, and peripheral blood. Moreover, the depletion of Gr-1(+) MDSCs abrogated the protective effect and immune suppression function of GSK872 in ConA-induced IMH. Altogether, our data demonstrate that RIP3 blockade prevents ConA-induced IMH through promoting MDSCs infiltration. Inhibition of RIP3 kinase may be a novel therapeutic avenue for AIH treatment. |
format | Online Article Text |
id | pubmed-8692153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-86921532022-01-01 RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism Liu, Man Zhang, Hongxia Zhang, Lu Liu, Xin Zhou, Simin Wang, Xiaoyi Zhong, Weilong Zhang, Jie Wang, Bangmao Zhao, Jingwen Zhou, Lu Int J Biol Sci Research Paper Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and underlying mechanism in AIH are poorly understood. Here, we detected the increased expression and activation of RIP3 in livers of patients and animal models with AIH. The inhibition of RIP3 kinase by GSK872 prevented concanavalin A (ConA)-induced immune-mediated hepatitis (IMH) by reduced hepatic proinflammatory cytokines and immune cells including Th17 cells and macrophages. Further experiments revealed that RIP3 inhibition resulted in an increase in CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) with immunoregulatory properties in the liver, spleen, and peripheral blood. Moreover, the depletion of Gr-1(+) MDSCs abrogated the protective effect and immune suppression function of GSK872 in ConA-induced IMH. Altogether, our data demonstrate that RIP3 blockade prevents ConA-induced IMH through promoting MDSCs infiltration. Inhibition of RIP3 kinase may be a novel therapeutic avenue for AIH treatment. Ivyspring International Publisher 2022-01-01 /pmc/articles/PMC8692153/ /pubmed/34975327 http://dx.doi.org/10.7150/ijbs.65402 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Liu, Man Zhang, Hongxia Zhang, Lu Liu, Xin Zhou, Simin Wang, Xiaoyi Zhong, Weilong Zhang, Jie Wang, Bangmao Zhao, Jingwen Zhou, Lu RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
title | RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
title_full | RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
title_fullStr | RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
title_full_unstemmed | RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
title_short | RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
title_sort | rip3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692153/ https://www.ncbi.nlm.nih.gov/pubmed/34975327 http://dx.doi.org/10.7150/ijbs.65402 |
work_keys_str_mv | AT liuman rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhanghongxia rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhanglu rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT liuxin rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhousimin rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT wangxiaoyi rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhongweilong rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhangjie rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT wangbangmao rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhaojingwen rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism AT zhoulu rip3blockadepreventsimmunemediatedhepatitisthroughamyeloidderivedsuppressorcelldependentmechanism |