HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis

Groneberg, Marie; Hoenow, Stefan; Marggraff, Claudia; Fehling, Helena; Metwally, Nahla Galal; Hansen, Christian M.; Bruchhaus, Iris; Tiegs, Gisa; Sellau, Julie; Lotter, Hannelore

doi:10.1016/j.jhep.2021.09.020

Cited by 15 publications

(12 citation statements)

References 102 publications

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“…HIF-1a can participate in regulation cytokine expression Treg. Groneberg et al have demonstrated that HIF-1a induces IL-2 and Foxp3 expression in Treg, resulting in increased expression of IL-10 in Tregs (62). In the p e r i p h e r y , P D -L 2 c o s t i m u l a t i o n m a i n t a i n s T r e g immunosuppressive activity by inducing CPT1A expression.…”

Section: Involvement Of Metabolism In the Development Of Treg Cellsmentioning

confidence: 99%

The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity

et al. 2022

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Regulatory CD4+ T (Treg) cells play a key role in the induction of immune tolerance and in the prevention of autoimmune diseases. Treg cells are defined by the expression of transcription factor FOXP3, which ensures proliferation and induction of the suppressor activity of this cell population. In a tumor microenvironment, after transplantation or during autoimmune diseases, Treg cells can respond to various signals from their environment and this property ensures their suppressor function. Recent studies showed that a metabolic signaling pathway of Treg cells are essential in the control of Treg cell proliferation processes. This review presents the latest research highlights on how the influence of extracellular factors (e.g. nutrients, vitamins and metabolites) as well as intracellular metabolic signaling pathways regulate tissue specificity of Treg cells and heterogeneity of this cell population. Understanding the metabolic regulation of Treg cells should provide new insights into immune homeostasis and disorders along with important therapeutic implications for autoimmune diseases, cancer and other immune-system–mediated disorders.

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Section: Involvement Of Metabolism In the Development Of Treg Cellsmentioning

confidence: 99%

The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity

et al. 2022

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“…In this view, regulating the imbalance of Th17/Treg cells was identified as a potential therapeutic target for diseases. Arsenic trioxide [ 23 ], hypoxia-inducible factor (HIF-1α) [ 24 ], IL-21 [ 25 ], zinc [ 26 ], and other drugs have been proven to reverse the imbalance of Th17/Treg cells, playing a beneficial role in improving different disease models.…”

Section: Discussionmentioning

confidence: 99%

The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models

Wang,

Liu,

Zheng

et al. 2024

BMC Gastroenterol

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Background/aims Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. Methods PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. Results Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. Conclusion Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.

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“…In previous studies, regulating the imbalance of Th17/Treg cells was identi ed as a potential therapeutic target for diseases. Arsenic trioxide [23], hypoxia-inducible factor (HIF-1α) [24], IL-21 [25], zinc [26], and other drugs have been proved to regulate Th17 /Treg cells in different diseases, playing a bene cial role in improving disease models.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of The Low-dose IL-2 Through Targeting the Th17/Treg Axis in Primary Biliary Cholangitis Mice

Wang

Liu

Zheng

et al. 2023

Preprint

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Background/aims : Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. Methods PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mice were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. Results Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mice (P༜0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P༜0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mice, with decreased Treg cells, increased Th17 cells and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. Conclusion Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.

show abstract

HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis

Cited by 15 publications

References 102 publications

The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity

The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity

The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models

Therapeutic Potential of The Low-dose IL-2 Through Targeting the Th17/Treg Axis in Primary Biliary Cholangitis Mice

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