Abstract: PO1804
TLR9 Signaling Pathways in Nasal-Associated Lymphoid Tissue Have a Crucial Role in the Pathogenesis of IgA Nephropathy
Session Information
- Glomerular Diseases: IgA, C3G, and FSGS
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Kano, Toshiki, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Bunkyo-ku, Tokyo, Japan
- Suzuki, Hitoshi, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Bunkyo-ku, Tokyo, Japan
- Makita, Yuko, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Bunkyo-ku, Tokyo, Japan
- Fukao, Yusuke, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Bunkyo-ku, Tokyo, Japan
- Suzuki, Yusuke, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Bunkyo-ku, Tokyo, Japan
Background
The pathogenesis of IgA nephropathy (IgAN) is closely associated with dysregulation of mucosal immune system. However, it is unclear which nasal-associated lymphoid tissue (NALT) or gut-associated lymphatic tissue (GALT) is more involved in the pathogenesis of IgAN. In present study, we examined whether NALT or GALT is the major responsible site for the nephritogenic immune complexes in murine IgA nephropathy.
Methods
We examined the effect of broad-spectrum antibiotics in the IgAN onset ddY mice. In addition, we assessed disease phenotypes of the IgAN onset ddY mice housed in germ free condition (GF-ddY) and transferred to specific pathogen free (SPF) condition. The levels of aberrantly glycosylated IgA and IgG-IgA immune complexes (IC) in serum and supernatant of cultured cells purified from NALT and mesenteric lymph node (MLN) were measured using the IgAN onset and the quiescent ddY mice (each n=15). To identify dysregulation of mucosal immune response site in IgAN, NALT and GALT were immunized separately in GF-ddY mice, i.e., nasally challenged with TLR9 ligand (CpG-ODN) stimulation and fecal transplantation.
Results
Broad-spectrum antibiotics depleted microbiota efficiently, resulted in ameliorating clinicopathological changes in IgAN onset ddY mice. Moreover, the GF-ddY mice did not develop IgAN, meanwhile, the GF-ddY mice showed an aggravation of renal injury with mesangial IgA deposition after transferred to SPF condition. In the IgAN onset ddY mice, the levels of aberrantly glycosylated IgA and IgG-IgA IC in serum and supernatant of cultured cells purified from NALT are significantly higher than those in the quiescent ddY mice. However, the levels of supernatant aberrantly glycosylated IgA and IgG-IgA IC produced by cultured cells purified from MLN showed no significant difference between the IgAN onset and the quiescent ddY mice. Although the GF-ddY mice nasally immunized with CpG-ODN also showed an aggravation of renal injury with mesangial IgA deposition, the GF-ddY mice which received fecal transplant did not develop IgAN.
Conclusion
Present study indicated that the dysregulation of mucosal immune response due to exogenous antigen exacerbated the pathogenesis of IgAN. TLR9 signaling pathways in NALT may be mainly involved in the pathogenesis of IgAN.