CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both a signaling receptor responding to DAMPs and PAMPs, as well as a long chain free fatty acid transporter. Recent studies have indicated that CD36 can integrate cell signaling and metabolic pathways through its dual functions and thereby influence immune cell differentiation and activation, and ultimately help determine cell fate. Its expression along with its dual functions in both innate and adaptive immune cells contribute to pathogenesis of common diseases, including atherosclerosis and tumor progression, which makes CD36 and its downstream effectors potential therapeutic targets. This review comprehensively examines the dual functions of CD36 in a variety of immune cells, especially macrophages and T cells. We also briefly discuss CD36 function in non-immune cells, such as adipocytes and platelets, which impact the immune system via intercellular communication. Finally, outstanding questions in this field are provided for potential directions of future studies.

Immune protection and lasting memory are accomplished through the generation of phenotypically and functionally distinct CD8 T cell subsets. Understanding how these effector and memory T cells are formed is the first step in eventually manipulating the immune system for therapeutic benefit. In this review, we will summarize the current understanding of CD8 T cell differentiation upon acute infection, with a focus on the transcriptional and epigenetic regulation of cell fate decision and memory formation. Moreover, we will highlight the importance of high throughput sequencing approaches and single cell technologies in providing insight into genome-wide investigations and the heterogeneity of individual CD8 T cells.

Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue "unhelped" CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells "help" the CD8 response during chronic infection via IL-21-induced BATF expression.