Toshiro Seki

Expression of glucocorticoid receptor shows negative correlation with human B-cell engraftment in PBMC-transplanted NOGhIL-4-Tg mice

The humanized mouse system is a promising tool for analyzing human immune responses in vivo. Recently, we developed a new humanized mouse system using the severely immunodeficient NOD/Shi-scid-IL2rγnull (NOG)-hIL-4-Tg mouse, which enabled us to evaluate the human humoral immune response after peripheral blood mononuclear cell (PBMC) transplantation. However, the mechanism by which hIL-4 enhances antigen-specific IgG production in these mice is not clear. In this study, we analyzed the relationship between human lymphocyte subsets and the expression level of the glucocorticoid receptor (GR) to clarify the humoral immune condition in human PBMC-transplanted NOG-hIL-4 mice. The results showed that the human GR mRNA level was significantly lower in NOG-hIL-4-Tg splenocytes than in conventional NOG splenocytes after immunization. Whereas no obvious difference of the proportion of T helper-cell subsets was observed between the NOG and NOG-hIL-4-Tg mouse strains, the B-cell proportion and antigen-specific IgG concentration in plasma showed strong negative correlations with the GR mRNA level. These results suggest that the GR expression level was changed in PBMCs in the humanized NOG-hIL-4-Tg mice, which may support B-cell survival and function in the mouse system.

A case of subclinical primary aldosteronism and subclinical Cushing's syndrome without risk factors of cardiovascular disease

• The critical issue is why excessive aldosterone secretion did not affect the cardiovascular status of this patient. In this regard, Ito et al. recently reviewed several possible mechanisms of normotensive PA (termed subclinical PA) [ Ito Y, Takeda R, Takeda Y. Subclinical primary aldosteronism. Best Pract Res Clin Endocrinol Metab. 2012; 26: 485495.]. They demonstrated that five possibilities could explain the causes of this normotensive form of PA: (a) an early state of the disease, (b) a mild form of the disease, (c) a low spontaneous baseline blood pressure level, (d) low sodium intake and/or high consumption of green tea, or (e) a low body mass index (BMI).