Cargando…

Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases

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 transcripti...

Descripción completa

Detalles Bibliográficos
Autores principales: Chávez, Miranda D., Tse, Hubert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281042/
https://www.ncbi.nlm.nih.gov/pubmed/34276700
http://dx.doi.org/10.3389/fimmu.2021.703972
_version_ 1783722766113964032
author Chávez, Miranda D.
Tse, Hubert M.
author_facet Chávez, Miranda D.
Tse, Hubert M.
author_sort Chávez, Miranda D.
collection PubMed
description 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 RORγt 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.
format Online
Article
Text
id pubmed-8281042
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82810422021-07-16 Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases Chávez, Miranda D. Tse, Hubert M. Front Immunol Immunology 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 RORγt 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. Frontiers Media S.A. 2021-07-01 /pmc/articles/PMC8281042/ /pubmed/34276700 http://dx.doi.org/10.3389/fimmu.2021.703972 Text en Copyright © 2021 Chávez and Tse https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chávez, Miranda D.
Tse, Hubert M.
Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases
title Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases
title_full Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases
title_fullStr Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases
title_full_unstemmed Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases
title_short Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases
title_sort targeting mitochondrial-derived reactive oxygen species in t cell-mediated autoimmune diseases
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281042/
https://www.ncbi.nlm.nih.gov/pubmed/34276700
http://dx.doi.org/10.3389/fimmu.2021.703972
work_keys_str_mv AT chavezmirandad targetingmitochondrialderivedreactiveoxygenspeciesintcellmediatedautoimmunediseases
AT tsehubertm targetingmitochondrialderivedreactiveoxygenspeciesintcellmediatedautoimmunediseases