title: Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18.
abstract: Uric acid is released from damaged cells and serves as a danger signal that alerts the immune system to potential threats, even in the absence of microbial infection. Uric acid modulation of innate immune responses has been extensively studied, but the impact of this damage-associated molecular pattern on adaptive responses remains largely unknown. In this study, we report that, in the presence of NF-κB signaling, uric acid crystals were capable of stimulating dendritic cells to promote the release of cytokines associated with Th17 polarization. Accordingly, naive CD4(+) T cells cocultured with uric acid-treated dendritic cells differentiated toward the Th17 lineage. Th17 differentiation required the inflammasome-dependent cytokines IL-1α/β and IL-18 in both in vitro and in vivo models, and the inflammasome adaptor protein ASC and caspase-1 were essential for Th17 responses. Collectively, our findings indicate a novel role for the danger signal uric acid, in cooperation with NF-κB activation, in driving proinflammatory Th17 differentiation. Our data indicate that sterile inflammation shapes adaptive immunity, in addition to influencing early innate responses.
authors: Singapore Immunology Network, Agency for Science, Technology, and Research, Biopolis 138648, Singapore.
authors: Cristina
authors: C
authors: Conforti-Andreoni
authors: Roberto
authors: R
authors: Spreafico
authors: Hong Liang
authors: HL
authors: Qian
authors: Nicolas
authors: N
authors: Riteau
authors: Bernhard
authors: B
authors: Ryffel
authors: Paola
authors: P
authors: Ricciardi-Castagnoli
authors: Alessandra
authors: A
authors: Mortellaro
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006433:Hemocyanins / Q000276:immunology / Q000494:pharmacology; D058847:Inflammasomes / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D014527:Uric Acid / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D058847:Inflammasomes; D007375:Interleukin-1; D020382:Interleukin-18; D016328:NF-kappa B; D014527:Uric Acid; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin