Glucocorticoid receptor inhibits Th2 immune responses by down-regulating Pparg and Gata3 in schistosomiasis

被引:0
|
作者
Sun, Tao [1 ]
Bi, Xiaojuan [1 ]
Yang, Ning [1 ]
Zhang, Xue [1 ]
Chu, Jin [1 ]
Li, Liang [1 ]
Liu, Hui [1 ]
Tang, Rui [2 ]
Lin, Renyong [1 ]
机构
[1] Xinjiang Med Univ, Affiliated Hosp 1, Clin Med Res Inst, State Key Lab Pathogenesis Prevent & Treatment Hig, Urumqi, Xinjiang, Peoples R China
[2] Naval Med Univ, Dept Trop Infect Dis, Shanghai, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2025年 / 16卷
基金
中国国家自然科学基金;
关键词
glucocorticoid receptor; schistosomiasis; Pparg; Gata3; Th2 immune responses; T-HELPER TYPE-1; SINGLE-CELL; INTEGRATED ANALYSIS; PLASTICITY; FORMS;
D O I
10.3389/fimmu.2025.1518586
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction The Th2 immune response plays a pivotal role in the pathogenesis of schistosomiasis, contributing to the formation of hepatic granulomas and fibrosis. While the glucocorticoid receptor (GR) is a ubiquitously expressed nuclear receptor that mediates anti-inflammatory effects, its impact on Th2 responses in schistosomiasis remains underexplored. Thus, this study aimed to investigate the potential impact of GR activation on the hepatic Th2 immune response in schistosomiasis using the synthetic glucocorticoid dexamethasone.Method In vivo, Schistosoma japonicum-infected mice were treated with dexamethasone, while in vitro studies were conducted on Th2 cells. Additionally, RNA sequencing and single-cell sequencing were integrated to identify key transcription factors influenced by GR activation during Th2 cell differentiation, with gene expression levels validated both in vivo and in vitro.Results In vivo, GR activation markedly reduced the size of Schistosoma egg granulomas and substantially repressed the transcription of key Th2-related cytokines, such as IL-4, IL-5, and IL-13. In vitro, GR activation inhibited the transcription of IL-4, IL-5, and IL-13, as well as the secretion of IL-4 in Th2 cells. An integrated analysis of RNA sequencing and single-cell sequencing revealed that GR activation downregulated the expression of two major transcription factors, Gata3 and Pparg, which were elevated in infected mouse livers and Th2 cells but decreased following dexamethasone treatment.Conclusion GR activation may suppress the Th2 immune response triggered by egg antigens by downregulating the expression of the key transcription factors Gata3 and Pparg. While these findings provide insights into a potential complementary therapeutic strategy, further research is necessary to assess the feasibility and safety of targeting GR activation for the treatment of schistosomiasis.
引用
收藏
页数:11
相关论文
共 50 条
  • [21] CARMA1 Controls Th2 Cell-Specific Cytokine Expression through Regulating JunB and GATA3 Transcription Factors
    Blonska, Marzenna
    Joo, Donghyun
    Zweidler-McKay, Patrick A.
    Zhao, Qingyu
    Lin, Xin
    JOURNAL OF IMMUNOLOGY, 2012, 188 (07): : 3160 - 3168
  • [22] Gata3ZsG-fl: a novel murine Gata3 reporter allele revealed a unique expression profile of GATA3 controlled genes in ILC2 and Th2 under in vivo condition
    Gurram, Rama Krishna
    Wei, Danping
    Yu, Qiao
    Xi, Chen
    Cui, Kairong
    Hu, Gangqing
    Zheng, Mingzhu
    Chung, Hyunwoo
    Butcher, Matthew J.
    Zhao, Keji
    Liu, Chengyu
    Khillan, Jaspal S.
    Zhu, Jinfang
    JOURNAL OF IMMUNOLOGY, 2023, 210 (01):
  • [23] Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation
    Shinnakasu, Ryo
    Yamashita, Masakatsu
    Kuwahara, Makoto
    Hosokawa, Hiroyuki
    Hasegawa, Akihiro
    Motohashi, Shinichiro
    Nakayama, Toshinori
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (42) : 28216 - 28225
  • [24] Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci
    Yamashita, M
    Ukai-Tadenuma, M
    Miyamoto, T
    Sugaya, K
    Hosokawa, H
    Hasegawa, A
    Kimura, M
    Taniguchi, M
    DeGregori, J
    Nakayama, T
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (26) : 26983 - 26990
  • [25] Conditional deletion of Gata3 shows its essential function in TH1-TH2 responses
    Zhu, JF
    Min, B
    Hu-Li, J
    Watson, CJ
    Grinberg, A
    Wang, Q
    Killeen, N
    Urban, JF
    Guo, LY
    Paul, WE
    NATURE IMMUNOLOGY, 2004, 5 (11) : 1157 - 1165
  • [26] Conditional deletion of Gata3 shows its essential function in TH1-TH2 responses
    Jinfang Zhu
    Booki Min
    Jane Hu-Li
    Cynthia J Watson
    Alex Grinberg
    Qi Wang
    Nigel Killeen
    Joseph F Urban
    Liying Guo
    William E Paul
    Nature Immunology, 2004, 5 : 1157 - 1165
  • [27] The relationship of glucocorticoid receptor-beta expression to Th1 and Th2 responses in the skin
    Zweiman, B
    Hamid, Q
    Shimbara, A
    Leung, DYM
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 105 (01) : S267 - S267
  • [28] Uteroglobin suppresses allergen-induced TH2 differentiation by down-regulating the expression of serum amyloid A and SOCS-3 genes
    Ray, Rabindranath
    Zhang, Zhongjian
    Lee, Yi-Ching
    Gao, Ji-Liang
    Mukherjee, Anil B.
    FEBS LETTERS, 2006, 580 (25): : 6022 - 6026
  • [29] Generation of a novel GATA3 reporter and inducible deletion system to study GATA3hi Th2 and ILC2 cells in vivo
    Gurram, Rama Krishna
    Liu, Chengyu
    Zhu, Jinfang
    JOURNAL OF IMMUNOLOGY, 2019, 202 (01):
  • [30] Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation
    Drishti Tiwari
    Nancy Ahuja
    Sumit Kumar
    Rashi Kalra
    Ravikanth Nanduri
    Shalini Gupta
    Asheesh Kumar Khare
    Ella Bhagyaraj
    Rashmi Arora
    Pawan Gupta
    Cellular and Molecular Life Sciences, 2022, 79