Hsd11b1, also known as 11-beta-hydroxysteroid dehydrogenase-1, is an enzyme that converts inert glucocorticoids into active forms in tissues [1]. This function allows it to regulate tissue glucocorticoid levels, which are potent suppressors of immune responses. It is involved in multiple biological processes and associated with various pathways, such as the regulation of steroidogenesis and immune-related signaling pathways [1,2]. Genetic models, like gene knockout and over-expression models, are valuable for studying its functions.

In melanoma, Hsd11b1 was identified as a negative feedback mechanism in response to T cell immunotherapies. Enforced Hsd11b1 expression in mouse melanomas limited the efficacy of PD-1 blockade, while small molecule inhibitors improved responses in a CD8+ T cell-dependent manner. High levels of Hsd11b1, predominantly in tumor-associated macrophages, were associated with poor responses to ICI therapy in melanoma patients [1].

In bovine luteinized granulosa cells, progesterone modulates Hsd11b1-mediated cortisol production, with progestogens suppressing cortisol production by modulating Hsd11b1 expression [2].

In endometriosis, Hsd11b1 is upregulated in ectopic endometrial lesions and overexpression in dendritic cells and stromal cells may contribute to the disease by repressing myeloid dendritic cell maturation [3].

In mesenchymal stem cells, Hsd11b1 overexpression led to increased adipogenic differentiation and Hsd11b1 knockout enhanced osteogenic differentiation, showing its role in the switch from osteogenic to adipogenic differentiation [4].

In pancreatic adenocarcinoma, upregulation of Hsd11b1 promotes cortisol production and inhibits NK cell activation, and higher Hsd11b1 levels are related to poor prognosis [5].

In conclusion, Hsd11b1 is crucial for regulating glucocorticoid activation and has significant impacts on multiple biological processes and disease conditions. Gene knockout and over-expression models in mice have been instrumental in revealing its roles in diseases like melanoma, endometriosis, and pancreatic adenocarcinoma, highlighting its potential as a therapeutic target in these disease areas [1,3,4,5].