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

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

Apr 19, 2023 110 likes •319 views

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

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CD103+ dendritic cells elicit CD8+ T cell responses to accelerate kidney injury in Adriamycin nephropathy

Supervisor: Prof. David Harris

  • A. Supervisor: Dr. Yiping Wang
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Introduction

CD103+ DC

  • 1. Maintain tolerance by inducing Tregs
  • 2. Cross presentation to CD8 T cells

?

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

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Results

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A B C

Figure 1. Identification of CD103+ DCs in normal kidney

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D

Figure 1. Identification of CD103+ DCs in normal kidney

CD103: Green, CD11c: Red

Localizatioin of CD103+ DCs in kidney

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Figure 2. CD103+ DCs were increased in kidney of AN mice

Normal Week 1 Week 2 Week 4

A B

CD103 is predominantly expressed on CD11c+ DCs

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A

Figure 3. Depletion of CD103+ DC attenuate renal injury in AN mice. Normal AN+Vehicle AN+IgG-SAP AN+CD103-SAP CD103 CD11c

Day: 0 5 28 ADR Sacrifice CD103-SAP or IgG-SAP BALB/c

B

Figure 3. Depletion of CD103+ DC attenuate renal injury in AN mice

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Figure 3. Depletion of CD103+ DC attenuate renal injury in AN mice

D

Normal AN+Vehicle AN+IgG-SAP AN+CD103-SAP

C Renal function

Histology

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The mechanism underlying the pathogenic role of CD103+ DCs in AN ?

CD103+ DC CD8 T cells

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CD8 T OT-I CD4 T OT-II

Antigen presentation

Figure 4. Kidney CD103+ DCs preferably primed CD8 T cells.

CD103+ DCs CD103- DCs

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A

Figure 5. Activated CD103+ DCs co-localized with CD8 T cells in kidney of AN mice

CD103 CD4 CD103-CD4 Merged CD103 CD8 CD103-CD8 Merged

B

Localization of CD103+ DCs and CD4/CD8 T cells in AN kidney

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Renal function

A

Fig 6. Depletion of CD103+ DCs reduce renal injury in AN SCID mice treated with CD8 T cells

CD4 T cells or CD8 T cells Day: 0 5 7 28 ADR Sacrifice CD103-SAP SCID

B

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Normal AN+Vehicle AN+CD4 AN+CD8 AN+CD103-SAP AN+CD4+CD103-SAP AN+CD8+CD103-SAP

C

Fig 6. Depletion of CD103+ DCs reduce renal injury in AN SCID mice treated with CD8 T cells

D

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

A B

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

A B

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CD103+ dendritic cells elicit CD8+ T cell responses to accelerate kidney injury in Adriamycin nephropathy.

Necrosis Apoptosis DAMPs ADR CD103+ DCs CD8+ T cells Inflammation Tissue Injury TEC Qi Cao, et al. JASN 2015.

Summary Conclusion

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Acknowledgements CTRR

  • Prof. David Harris

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

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