PMID- 34276700
OWN - NLM
STAT- MEDLINE
DCOM- 20211217
LR  - 20231013
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated 
      Autoimmune Diseases.
PG  - 703972
LID - 10.3389/fimmu.2021.703972 [doi]
LID - 703972
AB  - Mitochondrial dysfunction resulting in oxidative stress could be associated with 
      tissue and cell damage common in many T cell-mediated autoimmune diseases. 
      Autoreactive CD4 T cell effector subsets (Th1,Th17) driving these diseases 
      require increased glycolytic metabolism to upregulate key transcription factors 
      (TF) like T-bet and RORgammat that drive differentiation and proinflammatory 
      responses. However, research in immunometabolism has demonstrated that 
      mitochondrial-derived reactive oxygen species (ROS) act as signaling molecules 
      contributing to T cell fate and function. Eliminating autoreactive T cells by 
      targeting glycolysis or ROS production is a potential strategy to inhibit 
      autoreactive T cell activation without compromising systemic immune function. 
      Additionally, increasing self-tolerance by promoting functional immunosuppressive 
      CD4 T regulatory (Treg) cells is another alternative therapeutic for autoimmune 
      disease. Tregs require increased ROS and oxidative phosphorylation (OxPhos) for 
      Foxp3 TF expression, differentiation, and anti-inflammatory IL-10 cytokine 
      synthesis. Decreasing glycolytic activity or increasing glutathione and 
      superoxide dismutase antioxidant activity can also be beneficial in inhibiting 
      cytotoxic CD8 T cell effector responses. Current treatment options for T 
      cell-mediated autoimmune diseases such as Type 1 diabetes (T1D), multiple 
      sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) 
      include global immunosuppression, antibodies to deplete immune cells, and 
      anti-cytokine therapy. While effective in diminishing autoreactive T cells, they 
      can also compromise other immune responses resulting in increased susceptibility 
      to other diseases and complications. The impact of mitochondrial-derived ROS and 
      immunometabolism reprogramming in autoreactive T cell differentiation could be a 
      potential target for T cell-mediated autoimmune diseases. Exploiting these 
      pathways may delay autoimmune responses in T1D.
CI  - Copyright (c) 2021 Chavez and Tse.
FAU - Chavez, Miranda D
AU  - Chavez MD
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL, United States.
FAU - Tse, Hubert M
AU  - Tse HM
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL, United States.
LA  - eng
GR  - P30 DK079626/DK/NIDDK NIH HHS/United States
GR  - R01 DK099550/DK/NIDDK NIH HHS/United States
GR  - R01 DK127497/DK/NIDDK NIH HHS/United States
GR  - T32 GM008111/GM/NIGMS NIH HHS/United States
GR  - R56 DK126456/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210701
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - *Autoimmune Diseases/immunology/therapy
MH  - Humans
MH  - *Lymphocyte Activation
MH  - Mitochondria/*immunology
MH  - Reactive Oxygen Species/*immunology
MH  - T-Lymphocytes, Regulatory/*immunology
PMC - PMC8281042
OTO - NOTNLM
OT  - T cell
OT  - autoimmunity
OT  - immunometabolism
OT  - mitochondria
OT  - reactive oxygen species
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/20 06:00
MHDA- 2021/12/18 06:00
PMCR- 2021/01/01
CRDT- 2021/07/19 05:52
PHST- 2021/05/01 00:00 [received]
PHST- 2021/06/18 00:00 [accepted]
PHST- 2021/07/19 05:52 [entrez]
PHST- 2021/07/20 06:00 [pubmed]
PHST- 2021/12/18 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.703972 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jul 1;12:703972. doi: 10.3389/fimmu.2021.703972. eCollection 
      2021.