Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Sci Immunol. 2020 Apr 3;5(46). doi: 10.1126/sciimmunol.aay9283.
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.
组织驻留记忆 T（T）细胞存在于全身各处，随时准备介导局部免疫反应。尽管研究已经确定了一种不依赖于位置的驻留的共同机制，但 T 细胞可能存在一定程度的专业化，以适应其特定的栖身组织。已经表明，皮肤中的 T 细胞依赖于摄取外源性脂肪酸来生存，并上调脂肪酸结合蛋白 4（FABP4）和 FABP5，作为其转录程序的一部分。然而，FABP 作为一个更大的同工型家族存在，不同的成员以组织特异性的方式被选择，以优化局部脂肪酸的可用性。在这里，我们表明，尽管各种组织中的 T 细胞广泛表达 FABP，但它们并不局限于 FABP4 和 FABP5。相反，T 细胞表现出不同的同工型使用模式，这些模式是由组织衍生的因素决定的。这些模式是可塑的，因为迁移到不同器官的 T 细胞会根据其新的位置调整其 FABP 表达。因此，这些结果表明 T 细胞驻留程序存在组织特异性的覆盖，包括针对 T 细胞栖身组织的特定 FABP 表达。
