Cargando…

Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity

PURPOSE: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms. METHODS: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Si...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, He, Zhu, Lei, Wang, Rong, Xie, Lihui, Chen, Yuxi, Duan, Runping, Liu, Xiuxing, Huang, Zhaohao, Chen, Binyao, Li, Zhaohuai, Wang, Xianggui, Su, Wenru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727319/
https://www.ncbi.nlm.nih.gov/pubmed/34967854
http://dx.doi.org/10.1167/iovs.62.15.31
_version_ 1784626498395701248
author Li, He
Zhu, Lei
Wang, Rong
Xie, Lihui
Chen, Yuxi
Duan, Runping
Liu, Xiuxing
Huang, Zhaohao
Chen, Binyao
Li, Zhaohuai
Wang, Xianggui
Su, Wenru
author_facet Li, He
Zhu, Lei
Wang, Rong
Xie, Lihui
Chen, Yuxi
Duan, Runping
Liu, Xiuxing
Huang, Zhaohao
Chen, Binyao
Li, Zhaohuai
Wang, Xianggui
Su, Wenru
author_sort Li, He
collection PubMed
description PURPOSE: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms. METHODS: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was conducted to analyze the immune cell profiles of CDLNs from normal, EAU, and IL-38-treated mice. RESULTS: Administration of IL-38 attenuated EAU symptoms and reduced the proportion of T helper 17 (Th17) and T helper 1 (Th1) cells in the retinas and CDLNs. In scRNA-seq analysis, IL-38 downregulated the IL-17 signaling pathway and reduced the expression of Th17 cell pathogenicity-related genes (Csf2 and Il23r), findings which were also confirmed by flow cytometry. In vitro, IL-38 reduced the granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation function of IL-23 and inhibited IL-23R expression in Th17 cells. Moreover, when co-cultured with Th17 cells, IL-38 prevented IL-23 production in antigen-presenting cells (APCs). CONCLUSIONS: Our data demonstrate the therapeutic effect of IL-38 on EAU, and suggest that the effect of IL-38 may be caused by dampening of the GM-CSF/IL-23R/IL-23 feedback loop between Th17 cells and APCs.
format Online
Article
Text
id pubmed-8727319
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-87273192022-01-14 Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity Li, He Zhu, Lei Wang, Rong Xie, Lihui Chen, Yuxi Duan, Runping Liu, Xiuxing Huang, Zhaohao Chen, Binyao Li, Zhaohuai Wang, Xianggui Su, Wenru Invest Ophthalmol Vis Sci Immunology and Microbiology PURPOSE: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms. METHODS: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was conducted to analyze the immune cell profiles of CDLNs from normal, EAU, and IL-38-treated mice. RESULTS: Administration of IL-38 attenuated EAU symptoms and reduced the proportion of T helper 17 (Th17) and T helper 1 (Th1) cells in the retinas and CDLNs. In scRNA-seq analysis, IL-38 downregulated the IL-17 signaling pathway and reduced the expression of Th17 cell pathogenicity-related genes (Csf2 and Il23r), findings which were also confirmed by flow cytometry. In vitro, IL-38 reduced the granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation function of IL-23 and inhibited IL-23R expression in Th17 cells. Moreover, when co-cultured with Th17 cells, IL-38 prevented IL-23 production in antigen-presenting cells (APCs). CONCLUSIONS: Our data demonstrate the therapeutic effect of IL-38 on EAU, and suggest that the effect of IL-38 may be caused by dampening of the GM-CSF/IL-23R/IL-23 feedback loop between Th17 cells and APCs. The Association for Research in Vision and Ophthalmology 2021-12-30 /pmc/articles/PMC8727319/ /pubmed/34967854 http://dx.doi.org/10.1167/iovs.62.15.31 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Immunology and Microbiology
Li, He
Zhu, Lei
Wang, Rong
Xie, Lihui
Chen, Yuxi
Duan, Runping
Liu, Xiuxing
Huang, Zhaohao
Chen, Binyao
Li, Zhaohuai
Wang, Xianggui
Su, Wenru
Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity
title Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity
title_full Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity
title_fullStr Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity
title_full_unstemmed Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity
title_short Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity
title_sort therapeutic effect of il-38 on experimental autoimmune uveitis: reprogrammed immune cell landscape and reduced th17 cell pathogenicity
topic Immunology and Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727319/
https://www.ncbi.nlm.nih.gov/pubmed/34967854
http://dx.doi.org/10.1167/iovs.62.15.31
work_keys_str_mv AT lihe therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT zhulei therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT wangrong therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT xielihui therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT chenyuxi therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT duanrunping therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT liuxiuxing therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT huangzhaohao therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT chenbinyao therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT lizhaohuai therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT wangxianggui therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity
AT suwenru therapeuticeffectofil38onexperimentalautoimmuneuveitisreprogrammedimmunecelllandscapeandreducedth17cellpathogenicity