Research ArticleT CELLS

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

See allHide authors and affiliations

Science Immunology  03 Apr 2020:
Vol. 5, Issue 46, eaay9283
DOI: 10.1126/sciimmunol.aay9283

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

The skinny on getting fat

When T cells take up residence in a tissue, adaption to the tissue is key for their survival. Here, Frizzell et al. have studied metabolic adaptation of tissue-resident memory T (TRM) cells at three different sites: skin, liver, and the small intestine. They report that TRM cells in each of tissues rely on distinct members of the fatty acid–binding protein (FABP) family of proteins for uptake of fatty acids. By transferring liver-resident TRM cells into naïve mice, they found that FABP expression of these TRM cells is reprogrammed by the tissue they end up seeding in the recipient mice. The studies add to the growing appreciation of immune cells as integral components of tissues they reside in.

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.

View Full Text

Stay Connected to Science Immunology