Inflammation, Chimiokines et Immunopathologie, INSERM UMR996, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92296, France.
US31-UMS3679, La Plateforme d'Histologie sous Immunopathologie de Clamart, Institut Paris-Saclay d'Innovation Thérapeutique, Clamart 92140, France.
J Immunol. 2019 Apr 15;202(8):2189-2194. doi: 10.4049/jimmunol.1801065. Epub 2019 Mar 8.
Neutrophils are essential during contact hypersensitivity (CHS), a common skin allergic disease. NF-E2-related factor-2 (Nrf2) is a key regulator of redox balance and skin homeostasis playing a protective role in CHS. In this study, we investigated Nrf2 role in neutrophil recruitment during the sensitization phase of CHS. Comparing wild-type and Nrf2 knockout mice, we demonstrated that Nrf2 regulated dinitrochlorobenzene-induced xenoinflammation, notably neutrophil recruitment to sensitized skin. Nrf2 protective role was associated with high expression of antioxidant genes (, , …) and decreased chemokine production (CCL2, CCL4, CCL11). Interestingly, skin sensitization induced CD36 upregulation in skin-resident macrophages. In vitro results confirmed that the transcription of gene in macrophages was dependent on Nrf2 and led to an improved capacity to phagocyte-damaged neutrophils by efferocytosis. Nrf2 emerges as a critical target in the sensitization phase of CHS regulating neutrophil recruitment and accumulation in the skin through antioxidant-dependent and -independent mechanisms.
中性粒细胞在接触超敏反应（CHS）中是必不可少的，CHS 是一种常见的皮肤过敏性疾病。NF-E2 相关因子-2（Nrf2）是氧化还原平衡和皮肤动态平衡的关键调节剂，在 CHS 中发挥保护作用。在这项研究中，我们研究了 Nrf2 在 CHS 致敏阶段中性粒细胞募集中的作用。通过比较野生型和 Nrf2 敲除小鼠，我们证明 Nrf2 调节二硝基氯苯诱导的异种炎症，特别是中性粒细胞向致敏皮肤的募集。Nrf2 的保护作用与抗氧化基因（、、……）的高表达和趋化因子产生（CCL2、CCL4、CCL11）的减少有关。有趣的是，皮肤致敏诱导皮肤驻留巨噬细胞中 CD36 的上调。体外结果证实，巨噬细胞中 基因的转录依赖于 Nrf2，并导致通过吞噬作用清除受损中性粒细胞的能力提高。Nrf2 作为 CHS 致敏阶段的一个关键靶点出现，通过抗氧化依赖和非依赖机制调节中性粒细胞在皮肤中的募集和积累。
