Role of selenium-containing proteins in T-cell and macrophage function.
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.
Carlson
Bradley A
BA
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. carlsonb@mail.nih.gov
Yoo
Min-Hyuk
MH
Shrimali
Rajeev K
RK
Irons
Robert
R
Gladyshev
Vadim N
VN
Hatfield
Dolph L
DL
Park
Jin Mo
JM
D000818:Animals; D000906:Antibodies / Q000097:blood; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007109:Immunity / Q000502:physiology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D012343:RNA, Transfer; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012643:Selenium / Q000276:immunology* / Q000378:metabolism; D017279:Selenocysteine / Q000235:genetics; D051140:Selenoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000906:Antibodies; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D051140:Selenoproteins; D017279:Selenocysteine; D012343:RNA, Transfer; D012643:Selenium