The NF-κB regulator Bcl-3 modulates inflammation during contact hypersensitivity reactions in radioresistant cells.
The NF-κB regulator Bcl-3 modulates inflammation during contact hypersensitivity reactions in radioresistant cells.
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DOI：
10.1002/eji.201444994
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发表时间：
2015-04
影响因子：
5.4
通讯作者：
Siebenlist, Ulrich
中科院分区：
文献类型：
--
作者：
Tassi, Ilaria;Rikhi, Nimisha;Claudio, Estefania;Wang, Hongshan;Tang, Wanhu;Ha, Hye-lin;Saret, Sun;Kaplan, Daniel H.;Siebenlist, Ulrich
BCL-3是IκB家族中的一个非典型成员。在细胞核中，bcl3作为p50/NF-κB1或p52/NF-κB2同源二聚体的辅助因子，以上下文相关的方式调节NF-κB调控的转录。BCL-3具有致瘤潜力，在宿主防御病原体方面起关键作用，已有报道根据疾病模型的不同而减轻或加剧炎症。然而，Bcl3的细胞特异性功能在很大程度上仍不清楚。在这里，我们探讨了Bcl3在接触性超敏(CHS)小鼠模型中的作用，该模型依赖于角质形成细胞和免疫细胞之间的相互作用。BCL-3缺陷小鼠表现出对恶唑酮的CHS反应加剧和延长。炎症增加与趋化因子CXCL2、CXCL9和CXCL10的产生增加相关，从而增加中性粒细胞和CD8+T细胞的募集。骨髓嵌合体实验表明，Bcl3降低CHS反应的能力依赖于辐射抵抗细胞中的Bcl3活性。角质形成细胞中Bcl3的特异性消融导致CXCL9和CXCL10的产生增加，并持续募集CD8+T细胞。这些发现表明，在CHS反应的后期，通过包括角质形成细胞在内的抗辐射细胞的作用来限制炎症，Bcl3是一个关键的参与者。
Bcl-3 is an atypical member of the IκB family. Bcl-3 functions as a cofactor of p50/NF-κB1 or p52/NF-κB2 homodimers in nuclei, where it modulates NF-κB-regulated transcription in a context-dependent way. Bcl-3 has tumorigenic potential, is critical in host defense of pathogens, and has been reported to ameliorate or exacerbate inflammation, depending on disease model. However, cell-specific functions of Bcl-3 remain largely unknown. Here, we explored the role of Bcl-3 in a contact hypersensitivity (CHS) mouse model, which depends on the interplay between keratinocytes and immune cells. Bcl-3-deficient mice exhibited an exacerbated and prolonged CHS response to oxazolone. Increased inflammation correlated with higher production of chemokines CXCL2, CXCL9 and CXCL10, and consequently increased recruitment of neutrophils and CD8+ T cells. Bone marrow chimera experiments indicated that the ability of Bcl-3 to reduce the CHS response depended on Bcl-3 activity in radioresistant cells. Specific ablation of Bcl-3 in keratinocytes resulted in increased production of CXCL9 and CXCL10 and sustained recruitment of specifically CD8+ T cells. These findings identify Bcl-3 as a critical player during the later stage of the CHS reaction to limit inflammation via actions in radioresistant cells, including keratinocytes.
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影响因子：
30.5
作者：
Merad, M;Manz, MG;Engleman, EG
通讯作者：
Engleman, EG
接触性超敏反应中朗格汉斯细胞和朗格林+真皮树突状细胞的功能冗余。
DOI：
10.1038/jid.2010.223
发表时间：
2010-12
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
37.3
作者：
Maldonado V;Melendez-Zajgla J
通讯作者：
Melendez-Zajgla J
影响因子：
5.5
作者：
Engeman, T;Gorbachev, AV;Fairchid, RL
通讯作者：
Fairchid, RL
影响因子：
6.5
作者：
Mori, Tomoko;Kabashima, Kenji;Tokura, Yoshiki
通讯作者：
Tokura, Yoshiki