Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


pDCs in SLE_FINAL.pdf (2.18 MB)

ETD Abstract Container

Abstract Header

Exploration of Pro- and Anti-inflammatory Effector Functions of Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus

Davison, Laura Marie
http://orcid.org/0000-0002-3932-5078
http://rave.ohiolink.edu/etdc/view?acc_num=case1434020206

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
Plasmacytoid dendritic cells (pDCs) are a distinctive cell type bridging the innate and adaptive immune responses. Deceivingly minor in number, comprising <0.5% of total peripheral blood mononuclear cells, the effector functions of pDCs endow them with the potential to be an extremely influential population. The most notable and well studied effector function of these cells classifies them as pro-inflammatory, as they have the ability to produce massive amounts of type I interferons (particularly interferon α, IFNα). Other more recent studies have identified a subset of pDCs capable of producing the enzyme indoleamine 2,3 dioxygenase (IDO), which inhibits the activation and proliferation of effector T cells and promotes the activity of regulatory T cells, giving pDCs the potential to act in an anti-inflammatory capacity. In mice, it is possible to subcategorize pDCs by expression of membrane-bound molecules SiglecH (SigH) and CD19. The SigH+ pDCs are the subset identified as natural interferon-producing cells, whereas the CD19+ population has the unique ability to express IDO. Although definitive evidence was not available until recently, pDCs have long been suspected to be pathogenic in the autoimmune disorder systemic lupus erythematosus (SLE) due to the role of IFNα in driving many characteristics of the disease. We show here that indeed, the SigH+ population of pDCs is instrumental in disease initiation as well as perpetuation in the murine lupus model B6.Nba2. A role for IDO in SLE was heretofore unexplored; however, given the significant accumulation of CD19+ pDCs in the B6.Nba2 mice, we aimed to determine whether their effector function of IDO expression could be at all implicated in disease. We show here that IDO levels are elevated and positively correlate with levels of CD19+ pDCs. We used two methods of IDO manipulation: genetic ablation (IDO1 deficiency) and chemical inhibition (1-D-MT treatment). We conclude that IDO1 deficiency results in elevated levels of autoantibodies over time while long-term chemical inhibition has no statistically significant effect on disease. Dual inhibition of IDO (1-D-MT treatment of IDO1-/-) in B6.Nba2 significantly impacts antibody response to exogenous antigen. Overall, these data indicate unique roles for pDC subsets in disease development in lupus-prone B6.Nba2 mice.
Trine Jørgensen, PhD (Advisor)
Alan Levine, PhD (Committee Chair)
Thomas Hamilton, PhD (Committee Member)
Robert Silverman, PhD (Committee Member)
143 p.
Immunology
systemic lupus erythematosus; plasmacytoid dendritic cells; auto-antibodies; interferon alpha; indoleamine 2,3-dioxygenase;

Recommended Citations

Citations

  • Davison, L. M. (2015). Exploration of Pro- and Anti-inflammatory Effector Functions of Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1434020206

    APA Style (7th edition)

  • Davison, Laura. Exploration of Pro- and Anti-inflammatory Effector Functions of Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus. 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1434020206.

    MLA Style (8th edition)

  • Davison, Laura. "Exploration of Pro- and Anti-inflammatory Effector Functions of Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1434020206

    Chicago Manual of Style (17th edition)

case1434020206
565
© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.
Release 3.2.12