Abstract: The past two years have brought great progress in the genetics of systemic lupus erythematosus (SLE) heralded by the publication of genome-wide association studies in humans and the identification of susceptibility genes in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. SLE is a complex disease in which defects in several functional pathways have been identified. Genetic variants in a number of genes in these pathways have now been directly associated with lupus in both species. These discoveries have lead to a better understanding of the mechanisms of disease, and offer potential novel target for therapeutic intervention. As a large number of susceptibility genes are identified, lupus genetics will focus on mechanistic and molecular studies, in which mouse models will continue to serve a pre-eminent role. ... Read more

Abstract: Systemic lupus erythematosus (SLE) is a common autoimmune disease with unclear etiology. Treatments for it often provide inadequate control of disease activity or are limited by side effects. Recent studies have shown that rapamycin can be an effective treatment in both murine lupus models and human SLE. We demonstrated that rapamycin could directly alter molecular abnormalities in SLE T cells related to calcium signaling but not mitochondrial function. However, in light of increased knowledge of the role of mammalian target of rapamycin (mTOR) signaling throughout the immune system, several other potential sites of rapamycin action have been revealed. Specifically, mTOR regulates the production of interferon-α and the maintenance of immune tolerance at the level of the regulatory T cell and the dendritic cell, and can promote Th2 versus Th1 immune responses. Thus mTOR offers a window into diverse facets of lupus pathogenesis as well as a unifying narrative in our understanding of the therapeutic efficacy of rapamycin in SLE. ... Read more

Abstract: Lupus is believed to be an autoimmune disease, affecting many more women than men. Patients develop immune responses to self DNA, omnipresent in the body. Estrogen and androgen are involved in the disease. Immunosuppression and sex hormone therapeutics are two major classes of drugs in clinical trials. ... Read more

Natural Killer T (NKT) cells are special T lymphocyte subpopulations that have important regulatory functions on several autoimmune diseases. They possess the characteristics of both natural killer (NK) cells and T cells. However, NKT cells are heterogeneous and are quite difficult to be defined precisely.

NKT cells can be identified by the NK marker and the specific T cell receptor they express, the specific antigen they recognize in context with the non-conventional major histocompatibility (MHC) molecule. Even though NKT cells exist in humans, they were not studied as extensively as in mice. NKT cells express NK cell surface marker CD161, which ... Read more