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

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 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 TRM cells in a range of tissue widely express FABPs, they are not restricted to FABP4 and FABP5. Instead, TRM cells show varying patterns of isoform usage that are determined by tissue-derived factors. These patterns are malleable because 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.

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

“…Tissue resident memory T cells show varying patterns of FABP isoform usage that is decided by tissue-derived factors. Tissue resident memory T cells including macrophages and other immunocytes, modify their FABP expression depending on the tissue in which they are located or relocated, suggesting that immunocytes including tissue resident memory T cells change their expression of FABP based on local conditions [96]. These results emphasize the crosstalk between resident T cells and other immunocytes (including macrophages) and the local tissues/cells in which they (immunocytes) are resident for which (for the cross talk to occur) they (immunocytes) need a specific type of bioactive lipid.…”

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

“…In contrast, siIEL CD8 + T RM express Fabp1, Fabp2, and Fabp6, but negligible Fabp4 and Fabp5. These differences in FABP expression are determined by tissue-derived signals, and by altering FABP expression, CD8 + T cells can adapt to different host tissues (143).…”

MAIT Cells in Barrier Tissues: Lessons from Immediate Neighbors

“…Tissue-resident but not circulating memory CD8 + T cells require these exogenous fatty acids for their survival, and upregulate transporters and fatty acid binding proteins (FABP) necessary for long term maintenance (100,101). FABP isoform expression is tissuespecific, shared among resident T RM , IEL, ILC and gdT cells, with T RM able to modulate isotype specific expression on relocation to a new environment (102); Fabp4 and Fabp5 expression are enriched among skin resident cells, whereas Fabp1 is enriched among liver resident cells, including invariant NKT cells. Endogenous fatty acid metabolism is also important in IL-17 producing T H 17 (103), with murine Tc17 cells and human IL-17 producing bronchoalveolar MAIT cells also enriched for genes in fatty acid and lipid metabolism (29,104).…”