Abstract: SA-PO613
The Role of Plasmacytoid Dendritic Cells in Pathogenesis of Systemic Lupus Erythematosus
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Kitai, Hiroki, Nagoya university, Nagoya, Japan
- Kato, Noritoshi, Nagoya university, Nagoya, Japan
- Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Funahashi, Yoshio, Nagoya University, Nagoya, Aichi, Japan
- Ishimoto, Takuji, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Kosugi, Tomoki, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Maeda, Takahiro, Nagasaki Univesity, Nagasaki, Japan
- Komatsu, Shintaro, Nagoya university, Nagoya, Japan
Background
Systemic Lupus Erythematosus (SLE) is an autoimmune disease accompanied by production and deposition of immune complexes (IC) in multiple organs. Especially in the kidney, lupus nephritis (LN) due to deposition of IC occurs in about 40-70% of SLE patients, and about 10-30% of these patients progress to end stage renal disease.
Plasmacytoid dendritic cells (pDCs) which recognize viral nucleic acids by endosomal toll-like receptor (TLR) 7/9 and secrete large amounts of IFN- I are considered as important mediators of antiviral responses, while inappropriate recognition of self nucleic acids with IFN- I responses is linked to autoimmunity.
Therefore, this subset of DCs are attracting an attention for novel therapeutic target. But so far, little is known about the mechanisms how pDCs contribute pathogenesis of SLE and LN.
TLR7 agonist, imiquimod (IMQ) induced mice SLE model is deeply involved with IFN- I secretion, and present LN which is similar to those of human. With this model, we investigated pathogenesis of SLE focusing on pDCs.
Methods
We isolated pDCs from spleen of 4weeks IMQ model, and performed miRNA array. We extracted miRNA which was up or down-regulated, and searched mRNAs target of these miRNAs on database. Then predicted mRNA targets were confirmed by qPCR. Using human pDCs cell line, CAL-1, we performed TLR7, 9 and IC stimulation experiment.
Results
As a target of miRNAs that shows down-regulation, we found zinc finger transcription factor: Kruppel-Like Factor 4 (KLF4). By qPCR, we confirmed that KLF4 was up-regulated in mice pDCs. Similar results were observed in the pristine-induced mice SLE model.
We found that the protein levels of KLF4 was also up-regulated in TLR7 stimulation group compare with control group.
Conclusion
The production of autoantibody in SLE requires sustained production of IFN- I, but the pathogenesis of sustained IFN- I production in pDCs is not fully understood.
From our study, it was suggested that the up-regulation of KLF4 in pDCs plays some roles in the pathogenesis of SLE. Further studies are needed to elucidate the precise roll of KLF4 in pDCs.