Local exchange of metabolites shapes immunity.

Immune cell differentiation and function depend on metabolic changes for the provision of energy and metabolites. Consequently, cellular metabolism relies on the availability of micronutrients such as vitamins and energy-rich sources including amino acids and fatty acids. The bone marrow controls the continuous production of blood cells and is thereby reliant on the sophisticated interplay of progenitor and mature immune cells with its stromal microenvironment. The significance of stromal subsets in immunopoiesis is undisputed; however, our current knowledge is limited to their role in the production and secretion of a variety of soluble proteins such as cytokines. In contrast, the role of the haematopoietic niche in controlling and providing nutrients such as fatty acids, amino acids and vitamins, which are required for immune cell differentiation and function, remains largely elusive. In this review, we summarize the current understanding of local nutritional exchange and control between immune and stromal cells in peripheral tissue and, when it is known, in the bone marrow. The parallels found between peripheral tissues and bone marrow stroma raises the question of how local metabolism is capable of influencing haematopoiesis and immunopoiesis. A better understanding of the local exchange of nutrients in the bone marrow can be used to improve immune cell formation during ageing, after haematopoietic stem cell transplantation and during immune challenge.