Proceedings of the Nutrition Society

3rd International Immunonutrition Workshop

Session 2: Micronutrients and the immune system

Role of selenium-containing proteins in T-cell and macrophage function

21–24 October 2009, 3rd International Immunonutrition Workshop, Platja D'Aro, Girona, Spain.

Bradley A. Carlsona1 c1, Min-Hyuk Yooa1, Rajeev K. Shrimalia1, Robert Ironsa1, Vadim N. Gladysheva2, Dolph L. Hatfielda1 and Jin Mo Parka3

a1 Molecular of Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

a2 Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA

a3 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA

Abstract

Selenium (Se) has been known for many years to have played a role in boosting the immune function, but the manner in which this element acts at the molecular level in host defence and inflammatory diseases is poorly understood. To elucidate the role of Se-containing proteins in the immune function, we knocked out the expression of this protein class in T-cells or macrophages of mice by targeting the removal of the selenocysteine tRNA gene using loxP-Cre technology. Mice with selenoprotein-less T-cells manifested reduced pools of mature and functional T-cells in lymphoid tissues and an impairment in T-cell-dependent antibody responses. Furthermore, selenoprotein deficiency in T-cells led to an inability of these cells to suppress reactive oxygen species production, which in turn affected their ability to proliferate in response to T-cell receptor stimulation. Selenoprotein-less macrophages, on the other hand, manifested mostly normal inflammatory responses, but this deficiency resulted in an altered regulation in extracellular matrix-related gene expression and a diminished migration of macrophages in a protein gel matrix. These observations provided novel insights into the role of selenoproteins in the immune function and tissue homeostasis.

(Online publication June 25 2010)

Correspondence:

c1 Corresponding author: Bradley A. Carlson, fax +1 301 435-4957, email carlsonb@mail.nih.gov