title: Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Bangxing
authors.initials: B
authors.lastname: Hong
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
authors.forename: Lisa
authors.initials: L
authors.lastname: Rollins
authors.forename: Lindsey
authors.initials: L
authors.lastname: Berry
authors.forename: Xue F
authors.initials: XF
authors.lastname: Huang
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D054421:Chemokine CCL21 / Q000235:genetics / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D020868:Gene Silencing; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054388:Receptors, CCR / Q000235:genetics / Q000276:immunology; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: C119309:CC chemokine receptor 9; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D047908:Intracellular Signaling Peptides and Proteins; D054388:Receptors, CCR; D054400:Receptors, CCR7; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse