Abstract: TH-PO030

Group 1 Innate Lymphoid Cell Is Involved in the Progress of Experimental Glomerulonephritis Inhibited by PPAR-Alpha

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Okabayashi, Yusuke, Nippon Medical School, Tokyo, Japan
  • Tsuboi, Nobuo, The Jikei University School of Medicine, Tokyo, Japan
  • Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, Japan
  • Shimizu, Akira, Nippon Medical School, Tokyo, Japan
  • Nagasaka, Shinya, Nippon Medical School, Tokyo, Japan
  • Sawada, Anri, Nippon Medical School, Tokyo, Japan
  • Aratani, Sae, Nippon Medical School, Tokyo, Japan
  • Katsuma, Ai, Nippon Medical School, Tokyo, Japan
  • Aoki, Michiko, Nippon Medical School, Tokyo, Japan
  • Kajimoto, Yusuke, Nippon Medical School, Tokyo, Japan
  • Kang, Dedong, Nippon Medical School, Tokyo, Japan
  • Kanzaki, Go, The Jikei University School of Medicine, Tokyo, Japan
Background

Both CD8+ lymphocytes (CD8+Lym) and macrophages (Mφ) associate with the progress of the anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) in a rat model. However, the profile of CD8+Lym has not been fully evaluated except that they do not express T-cell receptor. Previous studies have shown that peroxisome proliferator activated receptors (PPARs) have anti-inflammatory effects. This study evaluated the profile of CD8+Lym and the effect of PPARs on CD8+Lym.

Methods

Male Wister-Kyoto rats at 4 weeks of age were intravenously injected with 50μg anti-GBM antibodies on day 1 and divided into 7 groups and received fenofibrate (30, 100, 300mg/kg/day; PPARα agonist), pioglitazone (12.5, 50, 100mg/kg/day; PPARγ agonist) or vehicle once-daily from day 0. 24-hr urine samples were collected and the kidneys were harvested on day 8. Isolated glomeruli were analyzed by flow cytometry and quantitative RT-PCR (qRT-PCR) analysis.

Results

In immunofluorescence and flow cytometric analysis of isolated glomeruli, CD8+Lym that infiltrated into glomerulus were lineage negative cells (negative for T-cell, B-cell, dendritic cell, NK cell, Mφ and granulocyte markers). Both the treatments of PPAR agonists reduced the level of proteinuria, and the number of crescentic lesions and infiltrating Mφ dose dependently. Notably, fenofibrate showed greater reduction in infiltration of CD8+Lym than pioglitazone, which was associated with the decrease of T-bet and IFN-γ mRNA expression. Moreover, fenofibrate down-regulated inflammatory cytokines and chemokines mRNA expression. qRT-PCR analysis of CD8+Lym harvested by cell sorting revealed that CD8+Lym expressed IFN-γ mRNA more than Mφ.

Conclusion

The phenotype of CD8+Lym was consistent with characters of group 1 innate lymphoid cell (ILC) which were recently identified as the novel subset of innate immune cells that were lineage negative population and express T-bet and IFN-γ. In conclusion, we first identified that CD8+Lym involved in the progression of a rat anti-GBM GN is group 1 ILC and PPARα attenuates the crescent formation in anti-GBM GN through the inhibition of group 1 ILC infiltration into glomerulus.