Zbtb32, also known as ROG, FAZF, TZFP and PLZP, is a transcription factor. It plays crucial roles in various physiological processes, including metabolic adaptation, immune responses, and cell differentiation. It is involved in pathways such as the crosstalk with the glucocorticoid receptor (GR) in the hypothalamic-pituitary-adrenal (HPA) axis during starvation, and in the regulation of B cell, T cell, and natural killer (NK) cell functions [1,2,3,4,5,6,7,8]. Genetic models, like knockout (KO) mice, have been valuable in studying its functions.

In Zbtb32 -/- mice, the production of glucocorticoids (GCs) in response to starvation is impaired due to defective cholesterol import, as GR-mediated upregulation of adrenal Scarb1 gene expression is absent, leading to aberrations in metabolic adaptation and progressive weight gain [1]. In the immune system, Zbtb32 -/- mice show nearly 20-fold higher antigen-specific IgG2b levels during chronic murine cytomegalovirus infection, while IgA responses in the intestine are similar to controls [2]. Zbtb32 -/- memory B cell-mediated recall responses occur more rapidly and persist longer, and secondary bone marrow plasma cells have elevated expression of genes promoting cell cycle progression and mitochondrial function [3]. In anti-viral CD8+ T cells, Zbtb32 -/- mice show enhanced virus-specific CD8+ T cell responses and increased memory cell generation, but are more susceptible to systemic viral infection and lung pathology [6]. Also, Zbtb32 is essential for the proliferative burst and protective capacity of virus-specific NK cells, as it antagonizes the anti-proliferative factor Blimp-1 [7]. In NOD mice, loss of Zbtb32 did not significantly alter T cell responses, potentially due to compensation by homologous genes [4].

In conclusion, Zbtb32 is essential for metabolic adaptation to starvation through regulating adrenal GC production in crosstalk with GR. In the immune system, it restricts antibody responses during chronic viral infections, limits memory B cell recall responses, balances effector versus memory responses in CD8+ T cells, and controls the proliferative burst of virus-specific NK cells. The study of Zbtb32 using KO mouse models has enhanced our understanding of its functions in metabolism and immunity, providing insights into related disease mechanisms.