ABC Transporters in T Cell-Mediated Physiological and Pathological Immune Responses

Abstract

ATP-binding cassette (ABC) transporters represent a heterogeneous group of ATP-dependent transport proteins, which facilitate the import and/or export of various substrates, including lipids, sugars, amino acids and peptides, ions, and drugs. ABC transporters are involved in a variety of physiological processes in different human tissues. More recent studies have demonstrated that ABC transporters also regulate the development and function of different T cell populations, such as thymocytes, Natural Killer T cells, CD8⁺ T cells, and CD4⁺ T helper cells, including regulatory T cells. Here, we review the current knowledge on ABC transporters in these T cell populations by summarizing how ABC transporters regulate the function of the individual cell types and how this affects the immunity to viruses and tumors, and the course of autoimmune diseases. Furthermore, we provide a perspective on how a better understanding of the function of ABC transporters in T cells might provide promising novel avenues for the therapy of autoimmunity and to improve immunity to infection and cancer.

Keywords: ABC transporters; Immunometabolism; T cells; Th1 cells; Th17 cells; Th2 cells; allergy; autoimmunity; bacteria; fungi; immunity to infection; metabolism.

Figure 1

ATP-binding cassette (ABC) transporters represent a heterogeneous group of ATP-dependent transport proteins. (A) The illustration shows the structure of ABC transporters. (B) The cartoon provides an overview of typical ABC transporter substrates.

Figure 2

ABCG1 expression is high in double positive (DP) thymocytes and within the spleen. (A) Abcg1 expression for different T cell subpopulations shown as Expression Value normalized by DESeq2 and analyzed by using the ImmGen database and online platform (http://rstats.immgen.org/Skyline/skyline.html, accessed on 7 July 2021). (B) ABCG1 expression in different tissues analyzed by using the GENT2 platform to explore gene expression in normal and tumor tissues (http://gent2.appex.kr/gent2/, accessed on 7 July 2021).

Figure 3

ABC transporters regulate the function of different T cell populations. Abbreviations: NKT, Natural Killer T cell; Tfh cells, T follicular helper cells; Tfr cells, T follicular regulatory cells; GC, Germinal center; Tregs, regulatory T cells; Th cell, T helper cell. MDR1, Multidrug-resistance-protein-1; MPR4, Multidrug-resistance-associated-protein-4.