High Ambient Temperature Aggravates Experimental Autoimmune Uveitis Symptoms

作者全名："Pan, Su; Tan, Handan; Chang, Rui; Wang, Qingfeng; Zhu, Ying; Chen, Lin; Li, Hongxi; Su, Guannan; Zhou, Chunjiang; Cao, Qingfeng; Kijlstra, Aize; Yang, Peizeng"

作者地址："[Pan, Su; Tan, Handan; Chang, Rui; Wang, Qingfeng; Zhu, Ying; Chen, Lin; Li, Hongxi; Su, Guannan; Zhou, Chunjiang; Cao, Qingfeng; Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing Eye Inst,Chongqing Branch,Natl Clin Res, Chongqing, Peoples R China; [Kijlstra, Aize] Univ Eye Clin Maastricht, Maastricht, Netherlands"

通信作者："Yang, PZ (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing Eye Inst,Chongqing Branch,Natl Clin Res, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000637734000001

JCR分区：Q1

影响因子：5.5

年份：2021

卷号：9

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：experimental autoimmune uveitis; inflammation; fumaric acid; succinic acid; ambient temperature

摘要："Whether ambient temperature influences immune responses leading to uveitis is unknown. We thus tested whether ambient temperature affects the symptoms of experimental autoimmune uveitis (EAU) in mice and investigated possible mechanisms. C57BL/6 mice were kept at a normal (22 degrees C) or high temperature (30 degrees C) housing conditions for 2 weeks and were then immunized with human interphotoreceptor retinoid-binding protein (IRBP651-670) peptide to induce EAU. Histological changes were monitored to evaluate the severity of uveitis. Frequency of Th1 cells and Th17 cells was measured by flow cytometry (FCM). The expression of IFN-gamma and IL-17A mRNA was measured by real-time qPCR. The generation of neutrophil extracellular traps (NETs) was quantified by enzyme-linked immunosorbent assay (ELISA). Differential metabolites in the plasma of the mice kept in the aforementioned two ambient temperatures were measured via ultra-high-performance liquid chromatography triple quadrupole mass spectrometry quadrupole time of flight mass spectrometry (UHPLC-QQQ/MS). The differential metabolites identified were used to evaluate their effects on differentiation of Th1 and Th17 cells and generation of NETs in vitro. The results showed that EAU mice kept at high temperature experienced a more severe histopathological manifestation of uveitis than mice kept at a normal temperature. A significantly increased frequency of Th1 and Th17 cells in association with an upregulated expression of IFN-gamma and IL-17A mRNA was observed in the splenic lymphocytes and retinas of EAU mice in high temperature. The expression of NETs as evidenced by myeloperoxidase (MPO) and neutrophil elastase (NE), was significantly elevated in serum and supernatants of neutrophils from EAU mice kept at high temperature compared to the normal temperature group. The metabolites in the plasma from EAU mice, fumaric acid and succinic acid, were markedly increased in the high temperature group and could induce the generation of NETs via the NADPH oxidase-dependent pathway, but did not influence the frequency of Th1 and Th17 cells. Our findings suggest that an increased ambient temperature is a risk factor for the development of uveitis. This is associated with the induction of Th1 and Th17 cells as well as the generation of NETs which could be mediated by the NADPH oxidase-dependent pathway."

基金机构：National Natural Science Foundation Key Program [81930023]; Natural Science Foundation Major International (Regional) Joint Research Project [81720108009]; Chongqing Outstanding Scientists Project (2019); Chongqing Key Laboratory of Ophthalmology (CSTC)Natural Science Foundation Project of CQ CSTC [2008CA5003]; Chongqing Science and Technology Platform and Base Construction Program [cstc2014pt-sy10002]; Chongqing Chief Medical Scientist Project (2018)

基金资助正文："This study was supported by the National Natural Science Foundation Key Program (81930023), Natural Science Foundation Major International (Regional) Joint Research Project (81720108009), Chongqing Outstanding Scientists Project (2019), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), Chongqing Science and Technology Platform and Base Construction Program (cstc2014pt-sy10002), and the Chongqing Chief Medical Scientist Project (2018)."