Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype
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- Olivier Manches
- Cancer Institute, New York University Langone Medical Center, New York, NY 10016;
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- Melissa Victoria Fernandez
- Cancer Institute, New York University Langone Medical Center, New York, NY 10016;
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- Joel Plumas
- Immunologie et Immunotherapie des Cancers, U823, Institut National de la Santé et de la Recherche Médicale, 38700 La Tronche, France;
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- Laurence Chaperot
- Immunologie et Immunotherapie des Cancers, U823, Institut National de la Santé et de la Recherche Médicale, 38700 La Tronche, France;
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- Nina Bhardwaj
- Cancer Institute, New York University Langone Medical Center, New York, NY 10016;
書誌事項
- 公開日
- 2012-08-09
- DOI
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- 10.1073/pnas.1204032109
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p>HIV modulates plasmacytoid dendritic cell (pDC) activation via Toll-like receptor 7, inducing type I IFN and inflammatory cytokines. Simultaneously, pDCs up-regulate the expression of indoleamine 2,3 dioxygenase (IDO), which is essential for the induction of regulatory T cells (Tregs), which function to down-modulate immune activation. Here we demonstrate the crucial importance of the noncanonical NF-κB pathway in the establishment of this immunoregulatory phenotype in pDCs. In response to HIV, the noncanonical NF-κB pathway directly induces IDO and involves the recruitment of TNF receptor-associated factor-3 to the Toll-like receptor/MyD88 complex, NF-κB–inducing kinase-dependent IκB kinase-α activation, and p52/RelB nuclear translocation. We also show that pDC-induced Tregs can inhibit conventional DC (cDC) maturation partially through cytotoxic T-lymphocyte antigen (CTLA)-4 engagement. Furthermore, CTLA-4 induces IDO in cDCs in a NF-κB–inducing kinase-dependent way. These CTLA-4–conditioned cDCs can in turn induce Treg differentiation in an IDO-dependent manner. Thus, the noncanonical NF-κB pathway is integral in controlling immunoregulatory phenotypes of both pDCs and cDCs.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 109 (35), 14122-14127, 2012-08-09
Proceedings of the National Academy of Sciences