Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells
| Autor: | Si-Yi Chen, Xue F. Huang, Lindsey Berry, Lisa Rollins, Bangxing Hong, Xiao Tong Song |
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| Rok vydání: | 2011 |
| Předmět: |
Receptors
CCR7 medicine.medical_treatment HIV Infections Mice Transgenic Biology T-Lymphocytes Regulatory Proinflammatory cytokine Mice Receptors CCR Immune system T-Lymphocyte Subsets Immunity medicine Animals Humans Gene Silencing Tumor Necrosis Factor alpha-Induced Protein 3 Innate immune system Chemokine CCL21 Intracellular Signaling Peptides and Proteins HIV Dendritic Cells General Medicine Mice Inbred C57BL Vaccination Cysteine Endopeptidases Cytokine Immunology Systemic administration Signal transduction |
| Zdroj: | Journal of Clinical Investigation. 121:739-751 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci42656 |
| Popis: | Both mucosal and systemic immune responses are required for preventing or containing HIV transmission and chronic infection. However, currently described vaccination approaches are largely ineffective in inducing both mucosal and systemic responses. In this study, we found that the ubiquitin-editing enzyme A20--an inducible feedback inhibitor of the TNFR, RIG-I, and TLR signaling pathways that broadly controls the maturation, cytokine production, and immunostimulatory potency of DCs--restricted systemically immunized DCs to induce both robust mucosal and systemic HIV-specific cellular and humoral responses. Mechanistic studies revealed that A20 regulated DC production of retinoic acid and proinflammatory cytokines, inhibiting the expression of gut-homing receptors on T and B cells. Furthermore, A20-silenced, hyperactivated DCs exhibited an enhanced homing capacity to draining and gut-associated lymphoid tissues (GALTs) after systemic administration. Thus, this study provides insights into the role of A20 in innate immunity. This work may allow the development of an efficient HIV vaccination strategy that is capable of inducing both robust systemic and mucosal anti-HIV cellular and humoral responses. |
| Databáze: | OpenAIRE |
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