Organ-specific isoform selection of fatty acid binding proteins in tissue-resident lymphocytes

Abstract

Abstract Tissue-resident memory T (TRM) cells exist throughout the body where they are poised to mediate local immune responses. Although studies have defined a common mechanism of residency independent of location, there is likely to be a level of specialization that adapts TRM cells to their given tissue of lodgment. It has been shown that TRM cells in the skin rely on the uptake of exogenous fatty acids for their survival and upregulate fatty acid binding proteins (FABP) 4 and FABP 5 as part of their transcriptional program. However, FABPs exist as a larger family of isoforms with different members selected in a tissue-specific fashion that is optimized for local fatty acid availability. Here we show that although TRM cells in a range of tissue widely express FABPs, they are not restricted to FABP 4 and 5. Instead, TRM cells show varying patterns of isoform usage that are determined by tissue-derived factors. These patterns are malleable since TRM cells relocated to different organs modify their FABP expression in line with their new location. As a consequence, these results argue for tissue-specific overlays to the TRM cell residency program, including FABP expression that is tailored to the particular tissue of TRM cell lodgment.