The tissue metabolic environment in autoimmunity influences immune and nonimmune cells via fuelling cellular metabolism or through metabolic signalling. Intracellular metabolic sensors combine several environmental cues to control transcription, metabolism, and cell function. The function of each cell contributes to the concerted dysfunctional behaviour of a tissue in autoimmunity.

ABSTRACT

Autoimmunity causes damage to organs targeted by the effector function of the immune response. The dynamics of autoimmunity in human peripheral tissues are not well understood due to the limited access to tissue samples. As cellular metabolism controls immune function, studying the crosstalk between the environment and cells within a tissue may provide information on how the metabolism of immune cells drives autoimmunity in peripheral tissues. In this review, I discuss some of the work that explored the complexity of the tissue environment, its sensing by cells in the tissue, and the consequences this has on cell and tissue functions, highlighting implications for autoimmune diseases. I also suggest a framework to study immunometabolism in tissues, contextualizing the metabolic choices of immune cells within the diversity of the extracellular environment they encounter.