Immunometabolism dysregulations in lupus have multifactorial origins.

Contributing factors include genetics and chronic autoantigen stimulation.

Metabolites from dysbiotic microbiota may regulate immune-cell metabolism.

Autoimmune activation and altered cellular metabolism are deeply interconnected.

Novel metabolic targets have been identified as potential therapies in lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the overactivation of the immune system has been associated with metabolic alterations. Targeting the altered immunometabolism has been proposed to treat SLE patients based on their results obtained and mouse models of the disease. Here, we review the recent literature to discuss the possible origins of the alterations in the metabolism of immune cells in lupus, the dominant role of mitochondrial defects, technological advances that may move the field forward, as well as how targeting lupus immunometabolism may have therapeutic potential.

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