(no subject)
I'm leaving tomorrow.
It was odd walking away from the building for the last time... I mean, I'll probably never go back.
The poster session went well... the poster was fine.
I got an award for being a scholar athlete, so that was neat.
Everyone asked questions I could answer, minus some crazy french man who I couldn't understand anyway...
I'm going to post a picture of my poster and my abstract because my abstract makes me feel smart. You probably don't want to look at it because it's long and technicical, but I'm posting it anyway.
Mmmkay.
PARTICIPANT: Cassidy Kohlmoos
RESEARCH ADVISORS: Donna Thibault, Lowen Lee, Steven Chan, and Paul J. Utz
TITLE: Type-I IFN signaling through p48 is required for the development of anti-snRNP autoantibodies in the pristane model of lupus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation in multiple tissues. A single intraperitoneal injection of the mineral oil pristane results in a lupus-like disease in mice of different genetic backgrounds. Balb/c mice immunized with pristane develop autoantibodies directed against double-stranded DNA (dsDNA) and components of the U1 small nuclear ribonucleoprotein (U1-snRNP) complex, as well as kidney disease. Many studies have indicated a role for the type-I interferon (IFN-I) system in human and murine lupus. Interferon regulatory factor-9 (IRF-9), also called p48, forms a heterotrimeric complex with Stat1 and Stat2 upon ligation of IFN-Is to their receptor and is essential for the induction of several IFN-I inducible genes. We tested the hypothesis that IFN-I signaling through p48 is required for the development a lupus-like disease in the pristane model. p48 deficient (-/-) and control (+/+) Balb/c mice were immunized with pristane, and autoantibody production was characterized by Enzyme-Linked Immunosorbent Assay (ELISA) and Immunoprecipitation (IP). While, pristane induced anti-dsDNA antibodies in both +/+ and -/- mice, only +/+ mice developed high titers of anti-snRNP antibodies. Both +/+ and -/- mice immunized with pristane developed hypergammaglobulinemia, characterized by high levels of total IgG, IgM, IgG1, IgG2a, and IgG2b. However, pristane-immunized -/- mice had significantly lower levels of total IgG and IgG2a. Pristane induced proteinuria in a significant number of +/+ mice, but not in -/- mice. Interestingly, 70% of -/- mice developed severe ascites by 12 months following pristane immunization as compared to only 20% of +/+ mice. Finally, we tested the response of -/- mice to foreign antigens by immunizing with ovalbumin (OVA) in complete Freund’s adjuvant, and assessing the antibody response on day 27. OVA immunization induced high levels of OVA-specific antibodies in both +/+ and -/- mice; however the levels of IgG2a were significantly decreased in -/- mice. In conclusion, although p48 is dispensable for the development of anti-dsDNA antibodies, type-I IFN signaling through p48 is required for kidney disease and the production of anti-snRNP antibodies. This further indicates a role for type I IFNs in the pathogenesis of SLE.
It was odd walking away from the building for the last time... I mean, I'll probably never go back.
The poster session went well... the poster was fine.
I got an award for being a scholar athlete, so that was neat.
Everyone asked questions I could answer, minus some crazy french man who I couldn't understand anyway...
I'm going to post a picture of my poster and my abstract because my abstract makes me feel smart. You probably don't want to look at it because it's long and technicical, but I'm posting it anyway.
Mmmkay.
PARTICIPANT: Cassidy Kohlmoos
RESEARCH ADVISORS: Donna Thibault, Lowen Lee, Steven Chan, and Paul J. Utz
TITLE: Type-I IFN signaling through p48 is required for the development of anti-snRNP autoantibodies in the pristane model of lupus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation in multiple tissues. A single intraperitoneal injection of the mineral oil pristane results in a lupus-like disease in mice of different genetic backgrounds. Balb/c mice immunized with pristane develop autoantibodies directed against double-stranded DNA (dsDNA) and components of the U1 small nuclear ribonucleoprotein (U1-snRNP) complex, as well as kidney disease. Many studies have indicated a role for the type-I interferon (IFN-I) system in human and murine lupus. Interferon regulatory factor-9 (IRF-9), also called p48, forms a heterotrimeric complex with Stat1 and Stat2 upon ligation of IFN-Is to their receptor and is essential for the induction of several IFN-I inducible genes. We tested the hypothesis that IFN-I signaling through p48 is required for the development a lupus-like disease in the pristane model. p48 deficient (-/-) and control (+/+) Balb/c mice were immunized with pristane, and autoantibody production was characterized by Enzyme-Linked Immunosorbent Assay (ELISA) and Immunoprecipitation (IP). While, pristane induced anti-dsDNA antibodies in both +/+ and -/- mice, only +/+ mice developed high titers of anti-snRNP antibodies. Both +/+ and -/- mice immunized with pristane developed hypergammaglobulinemia, characterized by high levels of total IgG, IgM, IgG1, IgG2a, and IgG2b. However, pristane-immunized -/- mice had significantly lower levels of total IgG and IgG2a. Pristane induced proteinuria in a significant number of +/+ mice, but not in -/- mice. Interestingly, 70% of -/- mice developed severe ascites by 12 months following pristane immunization as compared to only 20% of +/+ mice. Finally, we tested the response of -/- mice to foreign antigens by immunizing with ovalbumin (OVA) in complete Freund’s adjuvant, and assessing the antibody response on day 27. OVA immunization induced high levels of OVA-specific antibodies in both +/+ and -/- mice; however the levels of IgG2a were significantly decreased in -/- mice. In conclusion, although p48 is dispensable for the development of anti-dsDNA antibodies, type-I IFN signaling through p48 is required for kidney disease and the production of anti-snRNP antibodies. This further indicates a role for type I IFNs in the pathogenesis of SLE.