Transcriptional Profiling for Innate Immunity Receptor CD36 in the Regulation of Endothelial Cell Immunity Via Fatty Acid Metabolism

PURPOSE The immune system of living being has evolved via the action of immune defense mechanism by utilizing the cells of innate and adaptive immunity. Among these cells endothelial cell (EC) Immunity are least studied. ECs are emerging as innate immune cells and have some adaptive immunity features as well. How these EC immune cells can contribute to the brain immunity when implicated by CD36 (an innate immune receptor) is widely unknown. METHODS To understand this question, we wanted to investigate how CD36 regulates EC immunity and therefore we created EC-specific CD36 knockout (KO) TRAP mice by using several transgenic mouse lines and a translating ribosome affinity purification (TRAP) technique. Mouse brain tissues were subjected to isolation of ribosome-bound mRNA in the endothelia directly in vivo for next generation of RNA-seq and transcriptional profiling. RESULTS By transcriptomic and transcriptional analysis of RNA-seq data, we observed significant upregulation in the mRNA levels of interleukin 10 (IL-10) and IL-16, among toll-like receptors (TLRs) that initiate the innate immune response, we found that TLR-8 was downregulated in CD36-deficient brain endothelia in the EC-specific CD36 KO TRAP mice and highly enriched gene signature involved in fatty acid (FA) metabolism including ACSM 5, acyl-CoA thioesterase 12 (ACOT12) and StarD5. Moreover, MAPK/Erk1/2 signaling pathway appeared to be activated. CONCLUSION In summary, this study reveals a novel role of CD36 in the regulation of EC immunological properties, in which FA metabolic pathways might contribute to the regulation via changes in the immunometabolism in ECs.