Organ-specific Isoform Selection of Fatty Acid-binding Proteins in Tissue-resident Lymphocytes

Tissue-resident memory T (T) 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 cells to their given tissue of lodgment. It has been shown that T 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 cells in a range of tissue widely express FABPs, they are not restricted to FABP4 and FABP5. Instead, T cells show varying patterns of isoform usage that are determined by tissue-derived factors. These patterns are malleable because T 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 cell residency program, including FABP expression that is tailored to the particular tissue of T cell lodgment.