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

Tissue-resident memory T (T_RM) 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 T_RM cells to their given tissue of lodgment. It has been shown that T_RM cells in the skin rely on the uptake of exogenous fatty acids for their survival and up-regulate fatty acid-binding protein 4 (FABP4) and FABP5 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 T_RM cells in a range of tissue widely express FABPs, they are not restricted to FABP4 and FABP5. Instead, T_RM cells show varying patterns of isoform usage that are determined by tissue-derived factors. These patterns are malleable because T_RM 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 T_RM cell residency program, including FABP expression that is tailored to the particular tissue of T_RM cell lodgment.