Metabolic Reprogramming and Longevity of Tissue-Resident Memory T Cells.

Tissue-resident memory T cells (T _RM ) persist in peripheral tissues for long periods of time in the absence of antigenic stimulation. Upon re-encounter with cognate antigen, T _RM trigger an immediate immune response at the local tissue microenvironment and provide the first line of host defense. T _RM have been reported to play significant roles in host antimicrobial infection, cancer immunotherapy, and pathogenesis of a number of human autoimmune diseases, such as psoriasis, vitiligo, and atopic dermatitis. T _RM display a distinct gene transcriptome with unique gene expression profiles related to cellular metabolism that is different from naive T cells (T _N ), central memory T cells (T _CM ), and effector memory T cells (T _EM ). Skin CD8 ⁺ T _RM upregulate expression of genes associated with lipid uptake and metabolism and utilize mitochondria fatty acid β-oxidation to support their long-term survival (longevity) and function. In this review, we will summarize the recent progresses in the metabolic programming of T _RM and will also discuss the potential to target the unique metabolic pathways of T _RM to treat T _RM -mediated diseases.