Kidney Week

Abstract: FR-PO1073

Targeting TH17 Plasticity in Immune Mediated Inflammatory Diseases

Session Information

• Glomerular Diseases: Immunology and Inflammation - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Author

• Soukou, Shiwa, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany

Shiwa Soukou,

Background

During T cell development, naive T cells can differentiate into effector T cells (e.g T_H1 and T_H17) or into regulatory T cells (e.g. Foxp3^NegT_R1 and Foxp3^Pos Treg cells). Originally every single CD4 T cell lineage was thought to be stable after differentiation and to represent a functional homogenous population of cells. Recent data suggest that CD4 T cells and T_H17 cells in particular, have higher plasticity in the brain and in the intestine, where T_H17 cells are able to convert into T_H1 cells and into T_R1 cells respectively.

Methods

To prove the conversion from TH17 cells towards TR1exTH17 and the role of TR1exTH17 cells in the kidneys of nephritic, we used Fate+ (Foxp3RFP IL-10eGFP IL-17AKata IL-17ACRE R26YFP mice) and IL17ACre IL10fl/fl mice. Mice were immunized with nephrotoxic sheep serum. Additionally we treated them with PBS or 15 µg of αCD3 monoclonal antibody (mAB) intraperitoneally (i.p.). Injections were done at day 8 and day 10 post immunization. The mice were analyzed 4 hours after the last injection. Multiparametric flow cytometric analysis was performed and clinical parameters were measured in urine and plasma. Moreover histological analysis was done using Periodic acid–Schiff (PAS) staining that detects polysaccharides and mucosubstances.

Results

We could show that spontaneous and induced conversion of TH17 cells into TR1exTH17 over the course of NTN induction take place. Furthermore induction of NTN in IL17ACre IL10fl/fl mice showed aggravated glomerulonephritis.

Conclusion

Our first aim was to demonstrate the existence of TR1exTH17 in the kidneys of nephritic mice. Moreover we showed that the regulatory fate of TH17 cells (IL-10 producing TH17 and TR1exTH17 cells) can play an important role. Furthermore preliminary data show that deletion of IL-10 production by TH17 and exTH17cells can result in aggravated outcome of GN. However whether kidney IL-10 producing Foxp3Neg CD4 T cells are a functional homogenous population of regulatory cells remains unknown and the molecular mechanism underlying the conversion of TH17 into TR1 cells remain to be discovered

Funding

• Government Support - Non-U.S.