CD103+ dendritic cells elicit CD8+ T cell responses to accelerate - PowerPoint PPT Presentation

CD103+ dendritic cells elicit CD8+ T cell responses to accelerate kidney injury in Adriamycin nephropathy Supervisor: Prof. David Harris A. Supervisor: Dr. Yiping Wang

Introduction 1. Maintain tolerance by inducing Tregs 2. Cross presentation to CD8 T cells CD103+ DC ?

Aim This study will define the role of CD103+ DCs in healthy and diseased kidney. Hypothesis CD103+ DCs present endogenous antigen to CD8+ T cells to induce renal injury in diseased kidney.

Results

Figure 1. Identification of CD103+ DCs in normal kidney A B C

Figure 1. Identification of CD103+ DCs in normal kidney D Localizatioin of CD103+ DCs in kidney CD103: Green, CD11c: Red

Figure 2. CD103+ DCs were increased in kidney of AN mice A Normal Week 1 Week 2 Week 4 B CD103 is predominantly expressed on CD11c+ DCs

Figure 3. Depletion of CD103+ DC attenuate renal injury in AN mice Figure 3. Depletion of CD103+ DC attenuate renal injury in AN mice. A CD103-SAP or IgG-SAP ADR Sacrifice BALB/c Day: 0 5 28 B Normal AN+Vehicle AN+IgG-SAP AN+CD103-SAP CD103 CD11c

Figure 3. Depletion of CD103+ DC attenuate renal injury in AN mice C Renal function D Histology Normal AN+Vehicle AN+IgG-SAP AN+CD103-SAP

The mechanism underlying the pathogenic role of CD103+ DCs in AN ? CD8 T cells CD103+ DC

Figure 4. Kidney CD103+ DCs preferably primed CD8 T cells. CD103+ DCs CD103- DCs CD8 T OT-I CD4 T OT-II Antigen presentation

Figure 5. Activated CD103+ DCs co-localized with CD8 T cells in kidney of AN mice A B Localization of CD103+ DCs and CD4/CD8 T cells in AN kidney CD103 CD4 CD103-CD4 Merged CD103 CD8 CD103-CD8 Merged

Fig 6. Depletion of CD103+ DCs reduce renal injury in AN SCID mice treated with CD8 T cells A CD103-SAP ADR Sacrifice CD4 T cells or CD8 T cells SCID Day: 0 5 7 28 B Renal function

Fig 6. Depletion of CD103+ DCs reduce renal injury in AN SCID mice treated with CD8 T cells C Normal AN+Vehicle AN+CD4 AN+CD8 AN+CD103-SAP AN+CD4+CD103-SAP AN+CD8+CD103-SAP D

Fig 7. Depletion of CD103+ DCs reduce activation of transfused CD8 T cells in AN SCID mice A B

Figure 8. CD103+ DCs are activated by kidney DAMPs in AN A B

Summary ADR CD103+ DCs TEC CD8+ T cells Inflammation Necrosis Tissue Injury Apoptosis DAMPs Conclusion CD103+ dendritic cells elicit CD8+ T cell responses to accelerate kidney injury in Adriamycin nephropathy. Qi Cao, et al . JASN 2015.

Acknowledgements CTRR CKR Funding Prof. David Harris A/P. Stephen Alexander NHMRC Dr Yiping Wang Yuan Min Wang Dr Guoping Zheng Jimmy Zhou Changqi Wang Dr Vincent Lee WMI Alvin Tan Ya Wang Maggie Wang Hanh Nguyen Yu Hong Ye Zhao Min Hu Qing Li Chenshi Wang