PMID- 28841779
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20211204
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 69
IP  - 12
DP  - 2017 Dec
TI  - Review: Metabolic Control of Immune System Activation in Rheumatic Diseases.
PG  - 2259-2270
LID - 10.1002/art.40223 [doi]
AB  - Metabolic pathways mediate lineage specification within the immune system through 
      the regulation of glucose utilization, a process that generates energy in the 
      form of ATP and synthesis of amino acids, nucleotides, and lipids to enable cell 
      growth, proliferation, and survival. CD4+ T cells, a proinflammatory cell subset, 
      preferentially produce ATP through glycolysis, whereas cells with an 
      antiinflammatory lineage, such as memory and regulatory T cells, favor 
      mitochondrial ATP generation. In conditions of metabolic stress or a shortage of 
      nutrients, cells rely on autophagy to secure amino acids and other substrates, 
      while survival depends on the sparing of mitochondria and maintenance of a 
      reducing environment. The pentose phosphate pathway acts as a key gatekeeper of 
      inflammation by supplying ribose-5-phosphate for cell proliferation and NADPH for 
      antioxidant defenses. Increased lysosomal catabolism, accumulation of branched 
      amino acids, glutamine, kynurenine, and histidine, and depletion of glutathione 
      and cysteine activate the mechanistic target of rapamycin (mTOR), an arbiter of 
      lineage development within the innate and adaptive immune systems. Mapping the 
      impact of susceptibility genes to metabolic pathways allows for better 
      understanding and therapeutic targeting of disease-specific expansion of 
      proinflammatory cells. Therapeutic approaches aimed at glutathione depletion and 
      mTOR pathway activation appear to be safe and effective for treating lupus, while 
      an opposing intervention may be of benefit in rheumatoid arthritis. Environmental 
      sources of origin for metabolites within immune cells may include microbiota and 
      plants. Thus, a better understanding of the pathways of immunometabolism could 
      provide new insights into the pathogenesis and treatment of the rheumatic 
      diseases.
CI  - (c) 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. 
      on behalf of American College of Rheumatology.
FAU - Perl, Andras
AU  - Perl A
AD  - State University of New York, Upstate Medical University, Syracuse.
LA  - eng
GR  - R01 DK078922/DK/NIDDK NIH HHS/United States
GR  - R34 AR068052/AR/NIAMS NIH HHS/United States
GR  - R01 AI122176/AI/NIAID NIH HHS/United States
GR  - R01 AI048079/AI/NIAID NIH HHS/United States
GR  - R21 AI061066/AI/NIAID NIH HHS/United States
GR  - R01 AI072648/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20171108
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GAN16C9B8O (Glutathione)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Glucose/metabolism
MH  - Glutathione/metabolism
MH  - Glycolysis/immunology
MH  - Humans
MH  - Immune System/*metabolism
MH  - Metabolic Networks and Pathways/*immunology
MH  - Rheumatic Diseases/immunology/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5711528
MID - NIHMS896105
EDAT- 2017/08/26 06:00
MHDA- 2017/12/12 06:00
PMCR- 2017/12/12
CRDT- 2017/08/26 06:00
PHST- 2017/04/03 00:00 [received]
PHST- 2017/07/25 00:00 [accepted]
PHST- 2017/08/26 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2017/08/26 06:00 [entrez]
PHST- 2017/12/12 00:00 [pmc-release]
AID - ART40223 [pii]
AID - 10.1002/art.40223 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2017 Dec;69(12):2259-2270. doi: 10.1002/art.40223. Epub 2017 
      Nov 8.