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Nrf2 expression driven by Foxp3 specific deletion of Keap1 results in loss of immune tolerance in mice.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-01-14 , DOI: 10.1002/eji.201948285 Patricia Klemm 1 , Anandhi Rajendiran 1 , Athanassios Fragoulis 2 , Christoph Wruck 2 , Angela Schippers 1 , Norbert Wagner 1 , Tobias Bopp 3 , Klaus Tenbrock 1 , Kim Ohl 1
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-01-14 , DOI: 10.1002/eji.201948285 Patricia Klemm 1 , Anandhi Rajendiran 1 , Athanassios Fragoulis 2 , Christoph Wruck 2 , Angela Schippers 1 , Norbert Wagner 1 , Tobias Bopp 3 , Klaus Tenbrock 1 , Kim Ohl 1
Affiliation
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The transcription factor Nrf2 regulates oxidative stress responses. However, the specific function of Nrf2 in Tregs, the central regulators of immune homeostasis, is unclear. Here, we report an unexpected but important role of Nrf2 in Tregs. Nrf2 expression driven by Foxp3 specific deletion of Keap1 resulted in an autoinflammatory phenotype with enhanced effector T cell activation and immune cell infiltrates in the lung. While early postnatal death of mice with Foxp3 specific deletion of Keap1 was most probably due to ectopic Foxp3cre expression and subsequent Keap1 deletion in epithelial cells, bone marrow chimeras suggest that Nrf2 activation intrinsically in Tregs contributes to a loss of Treg cells and diminished peripheral tolerance. Moreover, Nrf2 activation was associated with a loss of Foxp3 expression, but an enhanced glucose uptake and mTOR activity in Tregs, thus mimicking a metabolic phenotype that is associated with impaired lineage stability and cell functioning.
中文翻译：
由Keap1的Foxp3特异性缺失驱动的Nrf2表达导致小鼠免疫耐受丧失。
转录因子Nrf2调节氧化应激反应。但是，尚不清楚Nrf2在Tregs（免疫稳态的主要调节器）中的具体功能。在这里，我们报道了Nrf2在Tregs中出乎意料但重要的作用。由Keap1的Foxp3特异性缺失驱动的Nrf2表达导致自发炎表型，其效应T细胞活化增强，免疫细胞浸润到肺中。虽然Foxp3特异性缺失Keap1的小鼠在出生后早期死亡很可能是由于异位Foxp3cre表达和随后Keap1在上皮细胞中的缺失所致，但骨髓嵌合体提示Tregs内在的Nrf2激活会导致Treg细胞的丢失并降低外周耐受性。此外，Nrf2激活与Foxp3表达的丧失有关，
更新日期：2020-01-14
中文翻译：
由Keap1的Foxp3特异性缺失驱动的Nrf2表达导致小鼠免疫耐受丧失。
转录因子Nrf2调节氧化应激反应。但是，尚不清楚Nrf2在Tregs（免疫稳态的主要调节器）中的具体功能。在这里，我们报道了Nrf2在Tregs中出乎意料但重要的作用。由Keap1的Foxp3特异性缺失驱动的Nrf2表达导致自发炎表型，其效应T细胞活化增强，免疫细胞浸润到肺中。虽然Foxp3特异性缺失Keap1的小鼠在出生后早期死亡很可能是由于异位Foxp3cre表达和随后Keap1在上皮细胞中的缺失所致，但骨髓嵌合体提示Tregs内在的Nrf2激活会导致Treg细胞的丢失并降低外周耐受性。此外，Nrf2激活与Foxp3表达的丧失有关，
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