TY - JOUR
T1 - DHX15 is required to control RNA virus-induced intestinal inflammation
AU - Xing, Junji
AU - Zhou, Xiaojing
AU - Fang, Mingli
AU - Zhang, Evan
AU - Minze, Laurie J
AU - Zhang, Zhiqiang
N1 - Funding Information:
We thank Dr. Harry B. Greenberg (Stanford University) and Dr. Gabriel N??ez (University of Michigan) for providing the kind gifts of the Rotavirus EW strain and plasmid Flag-NLRP6, respectively. This work was supported by Lupus Research Alliance grant 519418 (to Z.Z.), National Institutes of Health grant R56AI148215 and R01AI155488 (to Z.Z.), and American Heart Association Career Development Award 20CDA35260116 (to J.X.). Methodology and investigation, J.X. X.Z. M.F. E.Z. and L.J.M.; conceptualization, writing, and funding acquisition, J.X. and Z.Z. The authors declare no competing interests.
Funding Information:
We thank Dr. Harry B. Greenberg (Stanford University) and Dr. Gabriel Núñez (University of Michigan) for providing the kind gifts of the Rotavirus EW strain and plasmid Flag-NLRP6, respectively. This work was supported by Lupus Research Alliance grant 519418 (to Z.Z.), National Institutes of Health grant R56AI148215 and R01AI155488 (to Z.Z.), and American Heart Association Career Development Award 20CDA35260116 (to J.X.).
Publisher Copyright:
© 2021 The Authors
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/22
Y1 - 2021/6/22
N2 - RNA helicases play critical roles in various biological processes, including serving as viral RNA sensors in innate immunity. Here, we find that RNA helicase DEAH-box helicase 15 (DHX15) is essential for type I interferon (IFN-I, IFN-β), type III IFN (IFN-λ3), and inflammasome-derived cytokine IL-18 production by intestinal epithelial cells (IECs) in response to poly I:C and RNA viruses with preference of enteric RNA viruses, but not DNA virus. Importantly, we generate IEC-specific Dhx15-knockout mice and demonstrate that DHX15 is required for controlling intestinal inflammation induced by enteric RNA virus rotavirus in suckling mice and reovirus in adult mice in vivo, which owes to impaired IFN-β, IFN-λ3, and IL-18 production in IECs from Dhx15-deficient mice. Mechanistically, DHX15 interacts with NLRP6 to trigger NLRP6 inflammasome assembly and activation for inducing IL-18 secretion in IECs. Collectively, our report reveals critical roles for DHX15 in sensing enteric RNA viruses in IECs and controlling intestinal inflammation.
AB - RNA helicases play critical roles in various biological processes, including serving as viral RNA sensors in innate immunity. Here, we find that RNA helicase DEAH-box helicase 15 (DHX15) is essential for type I interferon (IFN-I, IFN-β), type III IFN (IFN-λ3), and inflammasome-derived cytokine IL-18 production by intestinal epithelial cells (IECs) in response to poly I:C and RNA viruses with preference of enteric RNA viruses, but not DNA virus. Importantly, we generate IEC-specific Dhx15-knockout mice and demonstrate that DHX15 is required for controlling intestinal inflammation induced by enteric RNA virus rotavirus in suckling mice and reovirus in adult mice in vivo, which owes to impaired IFN-β, IFN-λ3, and IL-18 production in IECs from Dhx15-deficient mice. Mechanistically, DHX15 interacts with NLRP6 to trigger NLRP6 inflammasome assembly and activation for inducing IL-18 secretion in IECs. Collectively, our report reveals critical roles for DHX15 in sensing enteric RNA viruses in IECs and controlling intestinal inflammation.
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U2 - 10.1016/j.celrep.2021.109205
DO - 10.1016/j.celrep.2021.109205
M3 - Article
C2 - 34161762
SN - 2211-1247
VL - 35
SP - 109205
JO - Cell Reports
JF - Cell Reports
IS - 12
M1 - 109205
ER -