Immuno-metabolic reprogramming of T cell: a new frontier for pharmacotherapy of Rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by ongoing inflammation primarily affecting the synovial joint. This inflammation typically arises from an increase in immune cells such as neutrophils, macrophages, and T cells (TC). TC is recognized as a major player in RA pathogenesis. The involvement of HLA-DRB1 and PTPN-2 among RA patients confirms the TC involvement in RA. Metabolism of TC is maintained by various other factors like cytokines, mitochondrial proteins & other metabolites. Different TC subtypes utilize different metabolic pathways like glycolysis, oxidative phosphorylation and fatty acid oxidation for their activation from naive TC (T₀). Although all subsets of TC are not deleterious for synovium, some subsets of TC are involved in joint repair using their anti-inflammatory properties. Hence artificially reprogramming of TC subset by interfering with their metabolic status poised a hope in future to design new molecules against RA

Graphical Abstract

Naïve T cells (T0) primarily rely on oxidative phosphorylation (OXPHOS) within the mitochondria for their energy needs. Upon activation, they undergo a metabolic switch, favoring aerobic glycolysis for rapid ATP generation. This metabolic shift is crucial for their differentiation into effector T cells. The PI3K/AKT/mTOR pathway plays a key role in regulating T cell metabolism. Targeting this pathway can alter their metabolic status, impacting their differentiation and cytokine production. In Rheumatoid Arthritis (RA), aberrant T cell activation and cytokine release contribute to inflammation and disease progression. Modulating T cell bioenergetics through PI3K/AKT/mTOR inhibition offers a promising therapeutic strategy for controlling autoimmunity in RA

Keywords:

• T cell metabolism
• immunometabolism
• Rheumatoid arthritis
• T cell reprogramming
• cytokines

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Funding

The author(s) reported there is no funding associated with the work featured in this article.