Therapeutic perspectives on the metabolism of lymphocytes in patients with rheumatoid arthritis and systemic lupus erythematosus

ABSTRACT

Introduction

The activation of autoreactive T- and B-cells and production of autoantibodies by B cells are involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recently, the concept of ‘immunometabolism’ has attracted significant attention. Immune cells produce large amounts of energy in the form of ATP and biosynthesize biological components such as nucleic acids and lipids via metabolic reprogramming to activate, differentiate, and exert their functions.

Areas covered

While the mechanisms underlying the metabolism of CD4⁺ T cells in SLE have been extensively studied, the metabolic changes underlying B cell activation, differentiation, and function remain unclear. Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs. In this review, we summarize the current knowledge on the immunometabolic mechanisms involved in SLE and RA and discuss the potential novel therapeutic drugs.

Expert opinion

The intensity of activation of different immune cells and their metabolic kinetics vary in different autoimmune diseases; thus, understanding the disease- and cell-specific metabolic mechanisms may help in the development of clinically effective immunometabolism-targeting drugs.

KEYWORDS:

• rheumatoid arthritis
• systemic lupus erythematosus
• B cell
• T cell
• immunometabolism

Article Highlights

- Targeting immunometabolism may be a potential therapy for autoimmune diseases such as RA and SLE.

- Although the mechanisms regulating immunometabolism and their relevance to disease have been studied in detail, especially in T cells in SLE, these remain unknown in other immune cells such as B cells.

- Some drugs that target mTOR and AMPK have shown some efficacy and tolerability in clinical trials in patients with SLE, but have not yet led to therapeutic breakthroughs.

- It is important to understand in detail the immune cell- and disease-specific metabolic mechanism underlying the pathogenesis of autoimmune diseases.

- Since intracellular metabolism is a phenomenon that is ubiquitously observed in various cells of the human body, it is necessary to fully understand its impact on normal physiological functions and to take into account the occurrence of adverse events.

Author contributions

Shigeru Iwata wrote the manuscript. Yoshiya Tanaka reviewed and edited the manuscript.

Declaration of interest

Yoshiya Tanaka has received speaking fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, research grants from Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo and consultant fee from Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GSK, Abbvie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported in part by JSPS (Japan Society for the Promotion of Science) grant number #JP16K09928. .