Organ-specific isoform selection of fatty acid–binding proteins in tissue-resident lymphocytes
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.
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Supplementary Material
Summary
Materials and Methods
Fig. S1. Representative flow cytometric cell sorting gating strategies.
Fig. S2. Kinetics of FABP gene expression during TRM cell development.
Fig. S3. FABP gene expression in FABP1-deficient CD8+ TRM cells.
Fig. S4. FABP protein expression in endogenous populations and liver TRM cells.
Table S1. Raw data.
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Science Immunology
Volume 5 | Issue 46
April 2020
April 2020
Copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Submission history
Received: 4 August 2019
Accepted: 6 February 2020
Acknowledgments
This work was supported by a Howard Hughes Medical Institute and Bill & Melinda Gates International Research Scholarship (OPP1175796) to L.K.M. and National Health and Medical Research Council (NHMRC; APP1129711) to L.K.M. H.F. is supported by an NSF Graduate Research Fellowship and was supported by an NSF Graduate Research Opportunities Worldwide Fellowship. N.G.Z. is supported by FAPESP BEPE Scholarship (2019/12431-2). S.L.P. is supported by a Cancer Council Victoria Postdoctoral Fellowship. H.M. is supported by an Australian Research Council (ARC) Discovery Early Career Researcher Award (DE170100575). J.A.V. is supported by an NHMRC Principal Research Fellowship (1154502) and Program Grant (1113293). L.K.M. is a Senior Medical Research Fellow supported by the Sylvia and Charles Viertel Charitable Foundation. Author contributions: H.F., R.F., D.F., S.N.C., M.E., N.G.Z., B.v.S., S.C.-G., and S.L.P. performed experiments. H.F., R.F., F.R.C., and L.K.M. designed experiments. H.F. and R.F. analyzed data. J.A.V. and H.E.G.M. provided supervision. H.F., R.F., F.R.C., and L.K.M. prepared the manuscript. L.K.M. provided funding and led the research program. Competing interests: The authors declare that they have no competing financial interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials.
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Funding Information
Howard Hughes Medical Institute: OPP1175796
Bill and Melinda Gates Foundation: OPP1175796
National Health and Medical Research Council: APP1129711
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