Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387451191> ?p ?o ?g. }
- W4387451191 endingPage "223146" @default.
- W4387451191 startingPage "ard" @default.
- W4387451191 abstract "Objective Polymorphisms in the antifungal signalling molecule CARD9 are associated with ankylosing spondylitis (AS). Here, we investigated the cellular mechanism by which CARD9 controls pathogenic Th17 responses and the onset of disease in both experimental murine AS and patients. Methods Experiments in SKG, Card9 −/− SKG, neutrophil-deplete SKG mice along with in vitro murine, neutrophil and CD4 + T cell cocultures examined Card9 function in neutrophil activation, Th17 induction and arthritis in experimental AS. In AS patients the neutrophil: Bath Ankylosing Spondylitis Functional Index relationship was analysed. In vitro studies with autologous neutrophil: T cell cocultures examined endogenous CARD9 versus the AS-associated variant (rs4075515) of CARD9 in T cellular production of IL-17A. Results Card9 functioned downstream of Dectin-1 and was essential for induction of Th17 cells, arthritis and spondylitis in SKG mice. Card9 expression within T cells was dispensable for arthritis onset in SKG mice. Rather, Card9 expression controlled neutrophil function; and neutrophils in turn, were responsible for triggering Th17 expansion and disease in SKG mice. Mechanistically, cocultures of zymosan prestimulated neutrophils and SKG T cells revealed a direct cellular function for Card9 within neutrophils in the potentiation of IL-17 production by CD4 + T cells on TCR-ligation. The clinical relevance of the neutrophil-Card9-coupled mechanism in Th17-mediated disease is supported by a similar observation in AS patients. Neutrophils from HLA-B27 + AS patients expanded autologous Th17 cells in vitro , and the AS-associated CARD9 S12N variant increased IL-17A. Conclusions These data reveal a novel neutrophil-intrinsic role for Card9 in arthritogenic Th17 responses and AS pathogenesis. These data provide valuable utility in our future understanding of CARD9-specific mechanisms in spondyloarthritis ." @default.
- W4387451191 created "2023-10-10" @default.
- W4387451191 creator A5003626996 @default.
- W4387451191 creator A5010962261 @default.
- W4387451191 creator A5014994984 @default.
- W4387451191 creator A5033945055 @default.
- W4387451191 creator A5042829575 @default.
- W4387451191 creator A5046013095 @default.
- W4387451191 creator A5046079169 @default.
- W4387451191 creator A5046643619 @default.
- W4387451191 creator A5088206934 @default.
- W4387451191 date "2023-10-09" @default.
- W4387451191 modified "2023-10-15" @default.
- W4387451191 title "Card9/neutrophil signalling axis promotes IL-17A-mediated ankylosing spondylitis" @default.
- W4387451191 cites W1836791320 @default.
- W4387451191 cites W1936415473 @default.
- W4387451191 cites W1969668872 @default.
- W4387451191 cites W2002463060 @default.
- W4387451191 cites W2013277175 @default.
- W4387451191 cites W2026853694 @default.
- W4387451191 cites W2027342983 @default.
- W4387451191 cites W2033753616 @default.
- W4387451191 cites W2046579578 @default.
- W4387451191 cites W2046957298 @default.
- W4387451191 cites W2049069390 @default.
- W4387451191 cites W2078428843 @default.
- W4387451191 cites W2086099777 @default.
- W4387451191 cites W2099730228 @default.
- W4387451191 cites W2101180663 @default.
- W4387451191 cites W2107951685 @default.
- W4387451191 cites W2117569516 @default.
- W4387451191 cites W2117985944 @default.
- W4387451191 cites W2118434625 @default.
- W4387451191 cites W2119279196 @default.
- W4387451191 cites W2123617777 @default.
- W4387451191 cites W2135199713 @default.
- W4387451191 cites W2140333814 @default.
- W4387451191 cites W2153035768 @default.
- W4387451191 cites W2164500783 @default.
- W4387451191 cites W2269635885 @default.
- W4387451191 cites W2287887328 @default.
- W4387451191 cites W2293237200 @default.
- W4387451191 cites W2313428973 @default.
- W4387451191 cites W2734764199 @default.
- W4387451191 cites W2768943715 @default.
- W4387451191 cites W2804029398 @default.
- W4387451191 cites W2886946434 @default.
- W4387451191 cites W2887492487 @default.
- W4387451191 cites W2888962444 @default.
- W4387451191 cites W2896918994 @default.
- W4387451191 cites W2901928825 @default.
- W4387451191 cites W2939338779 @default.
- W4387451191 cites W2980214381 @default.
- W4387451191 cites W2986771189 @default.
- W4387451191 cites W3026027040 @default.
- W4387451191 cites W3041987830 @default.
- W4387451191 cites W3124312573 @default.
- W4387451191 cites W3142481314 @default.
- W4387451191 cites W3188371230 @default.
- W4387451191 cites W3207431937 @default.
- W4387451191 cites W4206565620 @default.
- W4387451191 cites W4211033155 @default.
- W4387451191 cites W4245492581 @default.
- W4387451191 cites W4361006297 @default.
- W4387451191 doi "https://doi.org/10.1136/ard-2022-223146" @default.
- W4387451191 hasPublicationYear "2023" @default.
- W4387451191 type Work @default.
- W4387451191 citedByCount "0" @default.
- W4387451191 crossrefType "journal-article" @default.
- W4387451191 hasAuthorship W4387451191A5003626996 @default.
- W4387451191 hasAuthorship W4387451191A5010962261 @default.
- W4387451191 hasAuthorship W4387451191A5014994984 @default.
- W4387451191 hasAuthorship W4387451191A5033945055 @default.
- W4387451191 hasAuthorship W4387451191A5042829575 @default.
- W4387451191 hasAuthorship W4387451191A5046013095 @default.
- W4387451191 hasAuthorship W4387451191A5046079169 @default.
- W4387451191 hasAuthorship W4387451191A5046643619 @default.
- W4387451191 hasAuthorship W4387451191A5088206934 @default.
- W4387451191 hasBestOaLocation W43874511911 @default.
- W4387451191 hasConcept C203014093 @default.
- W4387451191 hasConcept C2776914184 @default.
- W4387451191 hasConcept C2777077863 @default.
- W4387451191 hasConcept C2777402515 @default.
- W4387451191 hasConcept C47348012 @default.
- W4387451191 hasConcept C71924100 @default.
- W4387451191 hasConceptScore W4387451191C203014093 @default.
- W4387451191 hasConceptScore W4387451191C2776914184 @default.
- W4387451191 hasConceptScore W4387451191C2777077863 @default.
- W4387451191 hasConceptScore W4387451191C2777402515 @default.
- W4387451191 hasConceptScore W4387451191C47348012 @default.
- W4387451191 hasConceptScore W4387451191C71924100 @default.
- W4387451191 hasFunder F4320306127 @default.
- W4387451191 hasFunder F4320306227 @default.
- W4387451191 hasFunder F4320332161 @default.
- W4387451191 hasLocation W43874511911 @default.
- W4387451191 hasOpenAccess W4387451191 @default.
- W4387451191 hasPrimaryLocation W43874511911 @default.
- W4387451191 hasRelatedWork W1502374914 @default.