Intracellular metabolic pathways control immune tolerance

Abstract

Disorders such as obesity and type 2 diabetes have been linked to immune dysfunction, raising the possibility that metabolic alterations can be induced by or be a consequence of alterations in immunological tolerance. Here, we describe how intracellular metabolic signalling pathways can 'sense' host energy/nutritional status, and in response, modulate regulatory T (Treg) cell function. In particular, we focus on mammalian target of rapamycin (mTOR) signalling, and how stimuli such as nutrients and leptin activate mTOR in an oscillatory manner to determine Treg cell proliferation status. We propose that metabolic changes such as nutritional deprivation or overload could dictate the characteristics of the Treg cell compartment and subsequent downstream immune reactions.