Noncanonical NF-κB signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation

作者：Sander W. Tas, Margriet J. Vervoordeldonk, Najat Hajji, Joost H. N. Schuitemaker, Koen F. van der Sluijs, Michael J. May, Sankar Ghosh, Martien L. Kapsenberg, Paul P. Tak, Esther C. de Jong · 发表于：Blood · 年份：2007 · DOI：10.1182/blood-2006-11-056010 · 被引用次数：162 · 研究领域：Tryptophan and brain disorders、Dermatology and Skin Diseases、Immune Cell Function and Interaction

Ligation of CD40 on dendritic cells (DCs) induces early production of inflammatory mediators via canonical NF-kappaB signaling, as well as late expression of the anti-inflammatory enzyme indoleamine 2,3-dioxygenase (IDO) via unknown signal transduction. By selective blocking of either the canonical NF-kappaB pathway using the NEMO-binding domain peptide or the noncanonical NF-kappaB pathway by small interfering RNA, we demonstrate that IDO expression requires noncanonical NF-kappaB signaling. Also, noncanonical NF-kappaB signaling down-regulates proinflammatory cytokine production in DCs. In addition, selective activation of the noncanonical NF-kappaB pathway results in noninflammatory DCs that suppress T-cell activation and promote the development of T cells with regulatory properties. These findings reveal an important role of the noncanonical NF-kappaB pathway in the regulation of immunity.