Effects of glucocorticoids and estrogens on cells and functions of the immune system - Sam Okret

Hormonal effects on the immune system are more or less well known. An example of the former is the anti-inflammatory activity of glucocorticoids (GCs), although still not all molecular details have been elucidated. A less known topic is the role and regulation of the de novo synthesis of GCs locally in the thymus, were it seems to have a paracrine role regulating thymocyte homeostasis and T cell development. Less established is also the effect of estrogens on cells of the immune system and particularly on tumours originating from lymphoid cells. The research projects of the group aim to elucidate molecular mechanisms that are involved in regulating physiological GC and estrogen effects on the immune system.

Two main areas are studied:

1. Role and regulation of GCs locally produced in the thymus for T cell development and function.

We and others have demonstrated a de novo synthesis of GCs in several extra-adrenal tissues including the thymus, intestinal epithelium and the skin were the local synthesis seems to play an important role for cell development or local defence. We are particularly interested in the role and regulation of GCs locally produced in the thymus for T cell development and function. Furthermore, we are interested in signaling pathways and cross-talk mechanisms involved in the anti-inflammatory action of GCs. A main mechanism for the anti-inflammatory action of GCs is the cross-talk between GC signaling and the NF-κB signaling pathway. We perform studies to further understand the mechanisms in this cross-talk.

2. Understanding the antiproliferative and tumor inhibiting effects of estrogen receptor β (ERβ) agonists on malignancies of lymphoid origin.

Lymphomas are generally not considered as endocrine related diseases. However, epidemiological data clearly demonstrate a gender difference in incidence and prognosis and a possible impact of estrogens. We have demonstrated that several murine or human lymphomas do express ERβ and are highly sensitive to ERβ agonists that cause an inhibition of tumor growth in vivo (see figure and ref. 5). Using various techniques (xenograph and cell experiments, gene expression studies) we are studying the molecular mechanism responsible for this tumor inhibiting effect by ERβ agonists.

human lymphoma cells and treated with subcutaneous injections of the ERβ agonist DPN

Immunocompromised mice were injected with human lymphoma cells and treated with subcutaneous injections of the ERβ agonist DPN.

Group members


Senior researcher

Konstantin Yakimchuk

Phone: +46-(0)8-585 837 34
Organizational unit: Okret
E-mail: Konstantin.Yakimchuk@ki.se

Array


Professor

Sam Okret

Phone: +46-(0)8-524 810 69
Organizational unit: Department of Biosciences and Nutrition (BioNut), H2
E-mail: Sam.Okret@ki.se

Senior lab manager

Mattias Berglund

Phone: +46-(0)8-534 811 13
Organizational unit: Okret
E-mail: Mattias.Berglund@ki.se

HormonesImmunology