期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.633586
关键词
Nitric oxide; hypoxia; immunosuppression; HIF; myeloid cells; von Hippel-Lindau; Prolyl hydroxylase inhibitors
类别
资金
- Swedish Research Council (Vetenskapsradet) [2019-01485]
- Swedish Cancer Society (Cancerfonden) [CAN2018/808]
- Swedish Children's Cancer Society (Barncancerfonden) [PR2020-0075]
- Knut and Alice Wallenberg Foundation Scholars Award
- Wellcome Trust, UK [214283/Z/18/Z]
- Portuguese Foundation for Science and Technology (FCT) scholarship [SFRH/BD/115612/2016]
- Wellcome Trust [214283/Z/18/Z] Funding Source: Wellcome Trust
- Fundação para a Ciência e a Tecnologia [SFRH/BD/115612/2016] Funding Source: FCT
- Forte [2019-01485] Funding Source: Forte
- Swedish Research Council [2019-01485] Funding Source: Swedish Research Council
Activation of the HIF pathway in myeloid cells, either through genetic deletion or pharmacological inhibitors, can suppress T cell proliferation in myeloid cell/T cell culture, leading to a suppression of adaptive cell immune response.
Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part via the Hypoxia inducible (HIF) transcription factors. A number of drugs that act on the HIF pathway are currently in clinical use and it is important to evaluate how they act on immune cell function as part of a better understanding of how they will influence patient outcomes. We show here that increased activation of the HIF pathway, either through deletion of the negative regulator of HIF, the von Hippel-Lindau (VHL) gene, in myeloid cells, or through pharmacological inhibitors of VHL-mediated degradation of HIF, potently suppresses T cell proliferation in myeloid cell/T cell culture. These data demonstrate that both pharmacological and genetic activation of HIF in myeloid cells can suppress adaptive cell immune response.
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