Determinants of Tissue-Specific Metabolic Adaptation of T Cells

Metabolic reprogramming is a hallmark of T cell activation and function. As our understanding of T cell metabolism increases, so does our appreciation of its inherent complexity. The metabolic heterogeneity of T cells that reside in different locations, such as lymphoid and non-lymphoid tissues, presents a challenge to developing therapies that exploit metabolic vulnerabilities. The roots of metabolic heterogeneity are only beginning to be understood. Here, we propose four factors that contribute to the adaptation of T cells to their dynamic tissue environment: (1) functional status of T cells, (2) local factors unique to the tissue niche, (3) type of inflammation, and (4) time spent in a specific tissue. We review emerging concepts about tissue-specific metabolic reprogramming in T cells with particular attention to explain how such metabolic properties are used as an adaptation mechanism. Adaptation of immune cells to the local microenvironment is critical for their persistence and function. Here, Varanasi et al. review the role and types of metabolic adaptation acquired by T cells in tissues and how these adaptations might differ between tissue type, disease state, and functionality of a T cell.