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. 2020 Feb;250(2):170-182.
doi: 10.1002/path.5358. Epub 2019 Dec 2.

Fusobacterium nucleatum facilitates ulcerative colitis through activating IL-17F signaling to NF-κB via the upregulation of CARD3 expression

Yongyu Chen  1   2 , Yan Chen  1   2 , Pan Cao  1   2 , Wenhao Su  1   2 , Na Zhan  1   3 , Weiguo Dong  1   2
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Fusobacterium nucleatum facilitates ulcerative colitis through activating IL-17F signaling to NF-κB via the upregulation of CARD3 expression

Yongyu Chen et al. J Pathol. 2020 Feb.

Abstract

Accumulating evidence links Fusobacterium nucleatum with ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal inflammation in UC remains poorly defined. Here, we first examined the abundance and impact of F. nucleatum on disease activity in UC tissues. Next, we isolated a strain of F. nucleatum from UC tissues and explored whether F. nucleatum aggravates the intestinal inflammatory response in vitro and in vivo. We also examined whether F. nucleatum infection involves the NF-κB or IL-17F signaling pathways. Our data showed that F. nucleatum was enriched in 51.78% of UC tissues and was correlated with the clinical course, clinical activity and refractory behavior of UC (p < 0.05). Furthermore, we demonstrated that F. nucleatum promoted intestinal epithelial damage and the expression of the inflammatory cytokines IL-1β, Il-6, IL-17F and TNF-α. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) through NOD2 to activate the IL-17F/NF-κB pathway in vivo and in vitro. Thus, F. nucleatum orchestrates a molecular network involving CARD3 and IL-17F to control the UC process. Measuring and targeting F. nucleatum and its associated pathways will yield valuable insight into the prevention and treatment of UC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: CARD3; F. nucleatum; IL-17F; NF-κB; NOD2; gene regulation; gene targeting; intestinal inflammation; microbe; ulcerative colitis.

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References

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