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Abstract: FR-PO1073

Targeting TH17 Plasticity in Immune Mediated Inflammatory Diseases

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Author

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

During T cell development, naive T cells can differentiate into effector T cells (e.g TH1 and TH17) or into regulatory T cells (e.g. Foxp3NegTR1 and Foxp3Pos 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 TH17 cells in particular, have higher plasticity in the brain and in the intestine, where TH17 cells are able to convert into TH1 cells and into TR1 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.