Department of Inflammation and Immunity
Trine N. Jorgensen, Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 444-7454
Fax: (216) 444-9329
Our laboratory (established at the Institute in 2007) has over the years focused specifically on two aspects of lupus: The effect(s) of sex hormones on the immune system during initiation/progression of lupus-like disease in mice, and the specific role played by type I interferons.
Elevated levels of serum type I interferons have been identified as a major feature of lupus and current clinical trials are testing the efficacy of targeting type I interferons in SLE patients. Unfortunately, type I interferons are essential in our capacity to control viral and some bacterial infections, and thus a major concern of these treatments is a heightened susceptibility to such infections.
Spontaneous mouse models of autoimmunity includes the New Zealand hybrid ((NZB x NZW)F1) mouse model of systemic lupus erythematosus (SLE) and the congenic B6.Nba2 model, derived from the NZB strain. These proven models of SLE develops several manifestations similar to those seen in human patients. Of particular interest is the fact that predominantly female (NZB x NZW)F1 and (B6.Nba2 x NZW)F1 mice develop the disease, and that genetic deficiency in the type I interferon receptor prevents disease initiation and progression.
We have recently identified the SiglecH+ plasmacytoid dendritic cell as a key producer of type I interferon in B6.Nba2 mice and shown that specific ablation of this cell subset limits disease progression in these mice. Our current studies aim at identifying the cellular targets responsible for driving lupus pathogenesis in response to type I interferons. As such, we are studying the pathogenicity of different immune cell subsets using type I interferon receptor conditional knock out animals.
In other words ...
- Identification of cellular targets of type I interferon in mouse lupus-like disease
- Type I interferon-inducing signals in mouse lupus-like disease; hormonal and genetic influences
Madeline Patt; research student
Eva Lasota; research student
- Laura M. Davison and Trine N. Jørgensen. 2015.SiglecH+ plasmacytoid dendritic cells drive spontaneous lupus-like disease development in B6.Nba2 mice. Arthritis and Rheumatology 67:1012-1022
- Trine N. Jørgensen. 2015. Sex disparities in the Immune Response. Editorial. Cellular Immunology, 294:61-62.
- Abhishek Trigunaite, Ayesha Khan, Evan Der, Anne Song, Sanjay Varikuti and Trine N. Jørgensen. 2013. Gr1highCD11b+ cells suppress B cell differentiation and lupus-like disease in lupus-prone male mice. Arthritis & Rheumatism 65:2392-2402. PMID: 23754362. PMCID: in progress.
- Evan Der, Joana Dimo, Abhishek Trigunaite, Justin Jones and Trine N. Jørgensen. 2014. Gr1+ cells modulate immune response to antigen challenge in male BWF1 mice through suppression of germinal center formation. The Journal of Immunology, 192:1570-1576.
- Alexandria David, Abhishek Trigunaite, Megan K. MacLeod, Angela C. Johnson, Philippa Marrack, and Trine N. Jørgensen. 2014. Intrinsic autoimmune capacities of bone marrow and fetal liver cells from female New Zealand hybrid mice. Genes & Immunity, in press. Advanced Online Publication: doi:10.1038/gene.2014.2.
- Trine N. Jørgensen, Jennifer Alfaro, Hilda L. Enriquez, William M. Loo, Stephanie Atencio, Melanie R. Gubbels Bupp, Christina M. Mailloux, Troy Metzger, Shannon Flannery, Stephen J. Rozzo, Brian L. Kotzin, Mario Rosemblatt, María Rosa Bono and Loren D. Erickson. 2010 Development of murine lupus involves the combined genetic contribution of the SLAM and Fc?R intervals within the Nba2 susceptibility locus. The Journal of Immunology 2010, 184:775-786.
- Trine N. Jørgensen, Ellen Roper, Joshua M. Thurman, Philippa Marrack, Brian L. Kotzin. 2007. Type I interferon signaling is involved in the spontaneous development of lupus-like disease in B6.Nba2 and (B6.Nba2 x NZW)F1 mice. Genes and Immunity 8:653-662.