From hepatic to hematopoietic: LRH-1's expanding cellular repertoire to the immune system

The nuclear receptor NR5A2 (Liver Receptor Homolog-1, LRH-1) has been well characterized in tissues of endodermal origin for the transcriptional control of development, metabolism, and steroidogenesis. In this minireview, we discuss the so far underappreciated expression and role of LRH-1 in hematopoietic cells. We further highlight how deregulation of LRH-1 may contribute to the pathogenesis of leukemia and immune cell-mediated diseases, and how targeting LRH-1 can be employed in immune cell-targeted therapies. Given that LRH-1 expression and function are highly tissue-specific, we further discuss how these contextual differences may be exploited to achieve therapeutic selectivity, especially focusing on the myeloid and T cell lineage. Although current evidence for LRH-1 functions in these immune cells is yet limited, its established role in the transcriptional regulation of development, differentiation, metabolism, proliferation, and cytokine expression of hematopoietic cells suggests a substantial and largely unexploited potential for therapeutic applications in leukemia and immunopathological diseases.