Immunosteroid as a regulator for Th1/Th2 balance: Its possible role in autoimmune diseases

Abstract

Immune balance controlled by Th1 and Th2 cells is critical for the protection of host from pathogenic invasion while its imbalance becomes the cause of various immune disorders including autoimmune diseases. Cytokines, such as IL-12 and IL-4, are critical factor to drive the differentiation of naïve CD4(+) T cells to Th1 or Th2 cells. In addition to cytokines, steroid hormones have been demonstrated to affect on the control of Th1/Th2 balance and the onset of autoimmune diseases. Here, we will propose a new concept that immunosteroid, which is designated as a steroid produced by immunoregulatory cells, also play a critical role for regulation of Th1/Th2 balance. First example of immunosteroid is Th2-dependently produced progesterone. Th2 cells, but not Th1 cells expressed P450scc and 20alpha-HSD and produced progesterone from 22R-hydroxycholesterol in cooperation with 3beta-HSD-expressing mouse fibroblasts. Th2-dependently produced progesterone induced apoptotic cell death of Th1 cells and inhibited the differentiation of Th1 cells. While Th2 cells were escaped from toxic effect of progesterone by metabolizing it to non-toxic 20alpha-hydroxyprogesterone with 20alpha-HSD. Second example of immunosteroid is dendritic cell (DC)-dependently produced 1alpha,25-dihydroxyvitamin D3 [1,25(OH)(2)D] secosteroid hormone, which has been demonstrated to inhibit autoimmune diseases. We found that 25-hydroxyvitamin D3 1alpha-hydroxylase, which metabolize 25-hydroxyvitamin D3 (inactive form) to 1,25(OH)(2)D was expressed in Th2-cytokine induced bone marrow-derived DC2 but not Th1-cytokine induced DC1. Moreover, 1,25(OH)(2)D was significantly inhibited DC1-induced type1 immunity. Thus, we initially demonstrated the critical role of immunosteroids in the control of Th1/Th2 balance influencing on the onset of autoimmune diseases. Therefore, it will be an important issue to investigate the possible role of immunosteroids for the regulation of autoimmune diseases.

Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development

“…Although these previous studies examined enzyme activities in vitro or cultured thymic cells (34,72), the present study fills an important gap by measuring endogenous corticosterone and cortisol levels in uncultured tissue. Taken together, the data raise the hypothesis that cortisol is synthesized de novo in the avian immune system as an "immunosteroid" (41), analogous to neurosteroids synthesized in the nervous system (10).…”

Recurrent pregnancy loss: TNF-α and IL-10 polymorphisms

“…Th1 and Th2 cells reciprocally regulate each other's function through their respective cytokines. [34] Th2 immune reactions support normal pregnancy, while Th1 immunity is considered detrimental to the fetus. [5] The chromosomal location of the gene controlling the secretion of tumor necrosis factor (TNF)-α (Th1) is 6p21.3.…”

Role of vasculature in atopic dermatitis

“…Thus the interaction of the cutaneous vascular system with the immune system remains a complex cascade and an exiting stage for future research (Table III). 4,11,12,17,24,[30][31][32][33][34][35][36] We thank Brigit Schneider for the excellent drawing of Figure 1.…”