Amino Acid Metabolism in Lupus

Kono, Michihito; Yoshida, Norimitsu; Tsokos, George C.

doi:10.3389/fimmu.2021.623844

Cited by 23 publications

(23 citation statements)

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“…The IKBKε inhibitor suppressed glycolysis and inhibited cancer cell growth. In recent years, cell metabolism has been found to be important for cell proliferation, differentiation, function, and cell death, and research on cell metabolism of immune cells is ongoing (33,34). So far, we have focused on cell metabolism of immune cells, especially T cells (35,36).…”

Section: Effect Of Ikbkε Inhibition On Microglial Activationmentioning

confidence: 99%

Inhibitor of NF‐κB Kinase Subunit ε Contributes to Neuropsychiatric Manifestations in Lupus‐Prone Mice Through Microglial Activation

Karino

Kono

Takeyama

et al. 2023

Arthritis & Rheumatology

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Objective Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiorgan dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30–40% of lupus patients and is the most severe presentation of SLE, frequently resulting in limitation of daily life. Recent studies have shown that microglia, tissue‐resident macrophages in the central nervous system, are involved in the pathogenesis of NPSLE. This study was undertaken to explore new therapeutic targets for NPSLE focusing on microglia. Methods RNA sequencing of microglia in MRL/lpr, lupus‐prone mice, as well as that of microglia cultured in vitro with cytokines were performed. A candidate gene, which could be a therapeutic target for NPSLE, was identified, and its role in microglial activation and phagocytosis was investigated using specific inhibitors and small interfering RNA. The effect of intracerebroventricular administration of the inhibitor on the behavioral abnormalities of MRL/lpr was also evaluated. Results Transcriptome analysis revealed the up‐regulation of Ikbke, which encodes the inhibitor of NF‐κB kinase subunit ɛ (IKBKε) in both microglia from MRL/lpr mice and cytokine‐stimulated microglia in vitro. Intracerebroventricular administration of an IKBKε inhibitor ameliorated cognitive function and suppressed microglial activation in MRL/lpr mice. Mechanistically, IKBKε inhibition reduced glycolysis, which dampened microglial activation and phagocytosis. Conclusion These findings suggest that IKBKε plays a vital role in the pathogenesis of NPSLE via microglial activation, and it could serve as a therapeutic target for NPSLE.

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Section: Effect Of Ikbkε Inhibition On Microglial Activationmentioning

confidence: 99%

Inhibitor of NF‐κB Kinase Subunit ε Contributes to Neuropsychiatric Manifestations in Lupus‐Prone Mice Through Microglial Activation

Karino

Kono

Takeyama

et al. 2023

Arthritis & Rheumatology

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“…Amino acids and products of metabolic processes determine the effector function of T cells (regulators, instigators of inflammation or effectors of cytotoxicity) and that is why may be linked to autoimmunity and related pathology. Amino acids influence immune response, because they are essential for the generation of building blocks needed for cell proliferation, the generation of energy by controlling metabolic pathways, the control of epigenetic pathways, the production of phospholipids and the control of oxidative stress [12]. Despite presenting the preliminary results, the authors are aware of significant study limitations.…”

Section: Resultsmentioning

confidence: 99%

Amino acids levels as a potential biomarker in myasthenia gravis

Kośliński¹,

Rzepiński²,

Koba³

et al. 2022

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The search for new diagnostic and therapeutic approaches for myasthenia gravis (MG) is highly desirable. Therefore, the aim of the present study is to assess the profile of non-essential amino acids in the serum of MG patients. We evaluated the serum levels of non-essential amino acids in MG patients (n = 10) and control subjects (CS, n = 10) using high-performance liquid chromatography (HPLC) method and assuming a two-fold concentration difference between the groups as significant. Serum levels of aspartic acid and glutamic acid in MG patients were significantly higher than in CS. There were no significant differences in mean serum levels of glycine, proline, alanine, serine, cysteine, arginine and tyrosine between MG patients and CS. The results indicate the need for further research to assess the role of non-essential amino acids in MG. Moreover, our preliminary results suggest that the metabolism of some amino acids seems to be changed in patients with MG. Therefore, we conclude that amino acids profiling might be helpful in searching for putative biomarkers of the central nervous system diseases such as myasthenia gravis.

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“…Apart from stemness signature, glycine/serine/threonine metabolism signature was also enriched in both SLE and renal cancer in cells of cluster 5 and 6 while it was obviously higher in SLE in cells of cluster 5 compared with renal cancer ( Figures 4 A and S7 A). Consistently, amino acid metabolism could affect T cell activation, differentiation, and function in both systemic lupus erythematosus ( Kono et al., 2021 ) and cancers ( Pan et al., 2021 ). Whereas, other tumorigenic signatures including angiogenesis and hypoxia, glycolysis, and metastasis were enriched in renal cancer cells of cluster either 5, 6, 10, 15, or 19 but not in SLE cells ( Figures 4 A and S7 B–S7E).…”

Section: Resultsmentioning

confidence: 99%