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Abstract: PO1452

Plasmacytoid Dendritic Cells from Murine IgA Nephropathy Have a Capacity to Enhance IgA Production Through TLR9/APRIL Signaling

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Fukao, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Hitoshi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Nakayama, Maiko, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Kano, Toshiki, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Makita, Yuko, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

Our recent study revealed that chronic Toll-like receptor 9 (TLR9) stimulation induce a proliferation-inducing ligand (APRIL) expression on naïve B cells and such APRIL+B cell may contribute to nephritogenic IgA production in IgA nephropathy (IgAN). On the other hand, APRIL from TLR9 activated dendritic cell (DC) is generally known to be involved in B cell maturation and IgA class switching. In this study, we evaluated IgA production through TLR9/APRIL signaling by DCs from murine IgAN.

Methods

Splenic B cells and DCs from grouped ddY (gddY) mice, which are known as the spontaneous IgAN model, and Balb/c mice were isolated using magnetic cell sorting system. In addition, DCs were further divided into three DC subsets; i.e., plasmacytoid DCs (pDCs), CD8+ conventional DCs (cDCs), and CD11b+ cDCs by cell sorter. We co-cultured these isolated DCs and B cells with or without CpG-ODN, a synthetic oligonucleotide TLR9 ligand, and IgA in the culture supernatants was measured by ELISA. We also measured the expressions of TLR9 and APRIL in each DC.

Results

The gddY-derived, but not Balb/c-derived, DCs could dramatically enhance IgA production by co-culture with B cells derived from both gddY and Balb/c mice, and further enhance under CpG-ODN stimulation. Moreover, pDCs from gddY mice strongly induced the IgA production in B cells, compared with cDCs. The expressions of APRIL and TLR9 in the pDCs were higher than those in cDCs.

Conclusion

Present findings suggest that the gddY DCs, especially pDCs, strongly enhance IgA synthesis from B cells through TLR9 and APRIL signaling.