PMID- 32541842
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20230203
IS  - 1935-3456 (Electronic)
IS  - 1933-0219 (Print)
IS  - 1933-0219 (Linking)
VI  - 14
IP  - 2
DP  - 2021 Mar
TI  - Dietary fiber metabolites regulate innate lymphoid cell responses.
PG  - 317-330
LID - 10.1038/s41385-020-0312-8 [doi]
AB  - Innate lymphoid cells (ILCs) rapidly undergo expansion in population size and 
      functional maturation in response to cytokines that signal infection, tissue 
      damage, or changes in physiology. Optimal ILC responses are shaped, in part, by 
      the microbiota but the mechanisms remain unclear. We report that short-chain 
      fatty acids (SCFAs), produced by the commensal microbiota from dietary fibers, 
      support optimal expansion of ILCs, including ILC1, ILC2, and ILC3 in the 
      intestines through their G-protein-coupled receptors (GPCRs). While this function 
      is primarily important for intestinal ILC populations, it can also boost ILC 
      responses in other tissues depending on host condition. ILCs express multiple 
      GPCRs that detect SCFAs. Interestingly, we found that the expression of SCFA 
      receptors, such as Ffar2 and Ffar3, by ILCs is induced by SCFAs. GPCR triggering 
      by SCFAs co-stimulates the activation of phosphoinositide 3-kinase (PI3K), Stat3, 
      Stat5, and mammalian target of rapamycin (mTOR), which is important for ILC 
      proliferation. While Ffar2 signaling promotes ILC2 proliferation, SCFAs can 
      suppress ILC2 proliferation through a non-Ffar2-mediated mechanism. In 
      conclusion, our findings indicate that SCFAs, as the major mediator of healthy 
      microbiota and nutritional status, function to maintain optimal numbers of ILCs 
      in peripheral tissues during infection and inflammatory responses.
FAU - Sepahi, Ali
AU  - Sepahi A
AD  - Laboratory of Immunology and Hematopoiesis, Mary H. Weiser Food Allergy Center, 
      School of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Liu, QingYang
AU  - Liu Q
AD  - Laboratory of Immunology and Hematopoiesis, Mary H. Weiser Food Allergy Center, 
      School of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Friesen, Leon
AU  - Friesen L
AD  - Laboratory of Immunology and Hematopoiesis, Mary H. Weiser Food Allergy Center, 
      School of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Kim, Chang H
AU  - Kim CH
AD  - Laboratory of Immunology and Hematopoiesis, Mary H. Weiser Food Allergy Center, 
      School of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. 
      chhkim@umich.edu.
AD  - Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, 
      MI, 48109, USA. chhkim@umich.edu.
AD  - Rogel Cancer Center, School of Medicine, University of Michigan, Ann Arbor, MI, 
      48109, USA. chhkim@umich.edu.
LA  - eng
GR  - R01 AI080769/AI/NIAID NIH HHS/United States
GR  - T32 HL007517/HL/NHLBI NIH HHS/United States
GR  - R01 AI121302/AI/NIAID NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - R01 DK076616/DK/NIDDK NIH HHS/United States
GR  - R01 AI074745/AI/NIAID NIH HHS/United States
GR  - R21 AI148898/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200615
PL  - United States
TA  - Mucosal Immunol
JT  - Mucosal immunology
JID - 101299742
RN  - 0 (Dietary Fiber)
RN  - 0 (FFAR3 protein, mouse)
RN  - 0 (Fatty Acids, Volatile)
RN  - 0 (Ffar2 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Dietary Fiber/*metabolism
MH  - Fatty Acids, Volatile/*metabolism
MH  - Immunity, Innate
MH  - Lymphocytes/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microbiota/*physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Receptors, G-Protein-Coupled/genetics/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction
MH  - Up-Regulation
PMC - PMC7736174
MID - NIHMS1600507
COIS- Disclosure: The authors declare no conflict of interest.
EDAT- 2020/06/17 06:00
MHDA- 2021/11/30 06:00
PMCR- 2021/03/13
CRDT- 2020/06/17 06:00
PHST- 2019/11/06 00:00 [received]
PHST- 2020/05/27 00:00 [accepted]
PHST- 2020/05/13 00:00 [revised]
PHST- 2020/06/17 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2020/06/17 06:00 [entrez]
PHST- 2021/03/13 00:00 [pmc-release]
AID - S1933-0219(22)00133-7 [pii]
AID - 10.1038/s41385-020-0312-8 [doi]
PST - ppublish
SO  - Mucosal Immunol. 2021 Mar;14(2):317-330. doi: 10.1038/s41385-020-0312-8. Epub 
      2020 Jun 15.