Abstract: TH-PO263
Natural IgM and TLR Agonists Switch Murine Splenic Pan-B to “Regulatory” Cells That Suppress Ischemia Induced Innate Inflammation via Regulating NKT-1 Cells
Session Information
- AKI Basic: Inflammation and Transcription
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Acute Kidney Injury
- 001 AKI: Basic
Authors
- Lobo, Peter I., University of Virginia, Charlottesvillle, Virginia, United States
- Schlegel, Kailo H., University of Virginia, Charlottesvillle, Virginia, United States
- Bajwa, Amandeep, University of Virginia, Charlottesvillle, Virginia, United States
- Okusa, Mark D., University of Virginia, Charlottesvillle, Virginia, United States
Background
Innate inflammation after reperfusion of ischemic organ has a significant role in ischemic acute kidney injury (AKI). In prior studies, we showed that natural IgM anti-leucocyte autoantibodies (IgM-ALA) inhibit inflammation. Here we show that pan-B cells are switched to regulatory cells when pretreated ex-vivo with either IgM or CpG.
Methods
C57BL/6 mice were i.v. infused with 0.5X10^6 B cells that were cultured for 48h with either IgM or CpG and 24h later these mice underwent bilateral renal ischemia. Plasma creatinine and other studies were preformed 24h after ischemia.
Results
Pre-treatment with regulatory pan-B cells (IgM or CpG treated) protected kidneys from AKI via regulation of in-vivo NKT-1 cells which amplify the innate inflammatory response to DAMPS released after ischemia. Such ex-vivo induced regulatory pan-B cells express low CD1d and inhibit inflammation by regulating in-vivo NKT-1 in the context of low lipid antigen presentation and by a mechanism that involves either PDL1. CpG induced regulatory B cells, but not IgM induced regulatory B cells, also require IL10 for their regulatory activity. LPS, unlike CpG, fails to down-regulate CD1d and switch pan-B to regulatory cells that inhibit ischemia induced AKI despite increased IL10 production.
Conclusion
Ex-vivo induced regulatory pan-B cells could have therapeutic relevance as these easily available cells can be pre-emptively infused to prevent AKI that can occur during open heart surgery or in transplant recipients receiving deceased donor organs.
Funding
- NIDDK Support