E-FABP: regulator of immune function

Fatty acids are essential for many aspects of biological activities. They function not only as an energy source but also as signaling molecules, regulating immune responses and other vital cellular functions. However, how to control fatty acid trafficking while sustaining lipid homeostasis inside cells remains largely unknown. As the main cytoplasmic lipid chaperones, fatty acid binding proteins (FABPs) are known to bind a variety of fatty acids and endogenous hydrophobic metabolites, facilitating lipid transportation and coordinating their responses [1]. Thus, FABPs are believed to play a central role in mediating metabolic balance and lipid-mediated responses through the regulation of diverse lipid signals. The FABP family consists of at least nine members of highly homologous proteins, each of which has been named according to the tissue where they were first cloned, such as adipose FABP (A-FABP) and intestinal FABP (I-FABP) [2]. While most FABP members display tightly-regulated patterns of tissue distribution, we noticed that epidermal FABP (E-FABP) is widely expressed in skin epidermal cells, vessel endothelial cells, and organ epithelial cells. Moreover, E-FABP is the predominant member of the FABP family which exists in various types of immune cells [3]. This ubiquitous expression pattern suggests that E-FABP is critical in maintaining cellular basic energy metabolism, thereby contributing to epithelial integrity and immune cell functions. In our research focusing on the role of E-FABP in tumor development, we found that mice deficient for E-FABP exhibited increased tumor growth and metastasis in different tumor models as compared to their wild-type counterparts [4]. To dissect the mechanisms of E-FABP in suppression of mammary tumor growth we have identified that tumor associated macrophages (TAMs), in particular a specific subset of TAMs which exhibit the CD11b + F4/80 + CD11c + MHCII + phenotype, highly express E-FABP and play a pivotal role in E-FABP-mediated protection against mammary tumor growth and metastasis. Furthermore, microarray analysis of genes expressed differentially in wild-type and E-FABP-/-macrophages demonstrated that E-FABP expression in TAMs strengthens interferon β (IFNβ) production and signaling. The E-FABP-regulated IFNβ responses can further recruit the infiltration of natural killer (NK) cells into the tumor microenvironment to enhance tumor killing activity. Thus, E-FABP is critical in regulating host immune responses to tumor challenges, and host expression of E-FABP may represent a new protective factor towards cancer prevention through enhancing anti-tumor activity of TAMs. However, everything has two sides. While host expression of E-FABP is able to inhibit tumor growth …