PMID- 29887373
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20230926
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 174
IP  - 2
DP  - 2018 Jul 12
TI  - A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling.
PG  - 271-284.e14
LID - S0092-8674(18)30591-9 [pii]
LID - 10.1016/j.cell.2018.05.014 [doi]
AB  - The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to 
      intestinal helminths and protists by tuft cell chemosensory-like sensing and 
      IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s 
      constitutively express the IL-25 receptor, which is negatively regulated by A20 
      (Tnfaip3). A20 deficiency in ILC2s spontaneously triggers the circuit and, 
      unexpectedly, promotes adaptive small-intestinal lengthening and remodeling. 
      Circuit activation occurs upon weaning and is enabled by dietary polysaccharides 
      that render mice permissive for Tritrichomonas colonization, resulting in luminal 
      accumulation of acetate and succinate, metabolites of the protist hydrogenosome. 
      Tuft cells express GPR91, the succinate receptor, and dietary succinate, but not 
      acetate, activates ILC2s via a tuft-, TRPM5-, and IL-25-dependent pathway. Also 
      induced by parasitic helminths, circuit activation and small intestinal 
      remodeling impairs infestation by new helminths, consistent with the phenomenon 
      of concomitant immunity. We describe a metabolic sensing circuit that may have 
      evolved to facilitate mutualistic responses to luminal pathosymbionts.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Schneider, Christoph
AU  - Schneider C
AD  - Department of Medicine, University of California San Francisco (UCSF), San 
      Francisco, CA 94143, USA.
FAU - O'Leary, Claire E
AU  - O'Leary CE
AD  - Department of Medicine, University of California San Francisco (UCSF), San 
      Francisco, CA 94143, USA.
FAU - von Moltke, Jakob
AU  - von Moltke J
AD  - Department of Medicine, University of California San Francisco (UCSF), San 
      Francisco, CA 94143, USA.
FAU - Liang, Hong-Erh
AU  - Liang HE
AD  - Department of Medicine, University of California San Francisco (UCSF), San 
      Francisco, CA 94143, USA.
FAU - Ang, Qi Yan
AU  - Ang QY
AD  - Department of Microbiology & Immunology, University of California San Francisco 
      (UCSF), San Francisco, CA 94143, USA.
FAU - Turnbaugh, Peter J
AU  - Turnbaugh PJ
AD  - Department of Microbiology & Immunology, University of California San Francisco 
      (UCSF), San Francisco, CA 94143, USA.
FAU - Radhakrishnan, Sridhar
AU  - Radhakrishnan S
AD  - Research Diets, Inc., New Brunswick, NJ 08901, USA.
FAU - Pellizzon, Michael
AU  - Pellizzon M
AD  - Research Diets, Inc., New Brunswick, NJ 08901, USA.
FAU - Ma, Averil
AU  - Ma A
AD  - Department of Medicine, University of California San Francisco (UCSF), San 
      Francisco, CA 94143, USA.
FAU - Locksley, Richard M
AU  - Locksley RM
AD  - Department of Medicine, University of California San Francisco (UCSF), San 
      Francisco, CA 94143, USA; Department of Microbiology & Immunology, University of 
      California San Francisco (UCSF), San Francisco, CA 94143, USA; Howard Hughes 
      Medical Institute, UCSF. Electronic address: richard.locksley@ucsf.edu.
LA  - eng
GR  - P01 HL107202/HL/NHLBI NIH HHS/United States
GR  - T32 DK007007/DK/NIDDK NIH HHS/United States
GR  - R01 HL122593/HL/NHLBI NIH HHS/United States
GR  - R37 AI026918/AI/NIAID NIH HHS/United States
GR  - R01 AI026918/AI/NIAID NIH HHS/United States
GR  - R01 HL128903/HL/NHLBI NIH HHS/United States
GR  - R01 AI030663/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180607
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Acetates)
RN  - 0 (Dietary Fiber)
RN  - 0 (GPR91 protein, mouse)
RN  - 0 (Il17rb protein, mouse)
RN  - 0 (Interleukins)
RN  - 0 (Mydgf protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-17)
RN  - 0 (TRPM Cation Channels)
RN  - 0 (Trpm5 protein, mouse)
RN  - AB6MNQ6J6L (Succinic Acid)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
SB  - IM
CIN - Cell. 2018 Jul 12;174(2):251-253. PMID: 30007413
MH  - Acetates/metabolism
MH  - Animals
MH  - Dietary Fiber/metabolism
MH  - Energy Metabolism
MH  - Epithelial Cells/cytology/metabolism/parasitology
MH  - Interleukins/genetics/metabolism
MH  - Intestinal Mucosa/cytology
MH  - Intestine, Small/microbiology/parasitology/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microbiota
MH  - Plasmids/genetics/metabolism
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Receptors, Interleukin/metabolism
MH  - Receptors, Interleukin-17/genetics/metabolism
MH  - Succinic Acid/metabolism
MH  - TRPM Cation Channels/metabolism
MH  - Tritrichomonas/growth & development/*metabolism
MH  - Tumor Necrosis Factor alpha-Induced Protein 3/genetics/metabolism
PMC - PMC6046262
MID - NIHMS970359
OTO - NOTNLM
OT  - A20
OT  - IL-25
OT  - ILC2s
OT  - TRPM5
OT  - Tritrichomonas
OT  - concomitant immunity
OT  - helminths
OT  - succinate
OT  - succinate receptor
OT  - tuft cells
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2018/06/12 06:00
MHDA- 2019/04/04 06:00
PMCR- 2019/07/12
CRDT- 2018/06/12 06:00
PHST- 2017/09/13 00:00 [received]
PHST- 2018/03/26 00:00 [revised]
PHST- 2018/05/07 00:00 [accepted]
PHST- 2018/06/12 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2018/06/12 06:00 [entrez]
PHST- 2019/07/12 00:00 [pmc-release]
AID - S0092-8674(18)30591-9 [pii]
AID - 10.1016/j.cell.2018.05.014 [doi]
PST - ppublish
SO  - Cell. 2018 Jul 12;174(2):271-284.e14. doi: 10.1016/j.cell.2018.05.014. Epub 2018 
      Jun 7.