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Abstract: PO1767

A Novel Inflammatory Dendritic Cell in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Ganesan, Latha Prabha, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Malvar, Ana, Hospital Fernandez, Buenos Aires, Argentina
  • Shapiro, John P., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Turman, James M., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Song, Huijuan, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Alberton, Valeria Gabriela, Hospital Fernandez, Buenos Aires, Argentina
  • Lococo, Bruno Jorge, Hospital Fernandez, Buenos Aires, Argentina
  • Madhavan, Sethu M., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Satoskar, Anjali A., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Birmingham, Daniel J., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Jarjour, Wael, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Group or Team Name

  • OSU Nephrology
Background

Progress in Lupus Nephritis (LN) management has been limited and treatment outcomes remain sub-optimal. Knowledge on intra-renal changes during LN flare and the major immune cells that drive local inflammatory damage will lead to improved outcomes in LN.

Methods

We performed transcriptomic analysis on serial kidney biopsies of proliferative LN (n=58). Glomeruli and Tubulointerstitium (TI) were isolated using LCM, and 580 immune transcripts were analyzed using Nanostring human immunology panel. Guided by transcriptomic analysis, multi-color, high-resolution confocal immunofluorescence (IF) analysis using antibodies against various immune cell markers, was performed on LN flare kidney biopsies (n=5) and healthy nephrectomy controls (n=5), to identify the dominant intra-renal immune cell phenotypes present during LN flare.

Results

Transcriptomic analysis identified Fc receptor gamma chain (FcRγ), to be the most significantly overexpressed glomerular immune transcript (Fold change (FC): 3.5, P=1E-10) and also overexpressed in the TI (FC: 1.7, P=0.001) compared to controls. Confocal IF analysis found FcRγ to be abundantly present in the peri-glomerular (PG) region and to a lesser extent in the TI during LN flare. FcRγ was weakly expressed in controls. Further IF analysis identified the phenotype of FcRγ expressing cells to be CD11c+,DC-SIGN+,MHC II+,CD64+,CD14+, CD16+,CD206-,CD68-,CD123-,CD3-,CD11b-. This signature aligns with a dendritic cell (DC) phenotype but distinct from plasmacytoid and conventional DC. It is most consistent with an inflammatory dendritic cell (infDC) phenotype. Importantly, confocal IF identified CD3+ T cells present in close proximity to PG infDC.

Conclusion

In this study, we identified a novel population of InfDC not previously described in LN. During LN flare, InfDC are present in abundance in the PG region. Their presence next to T cells suggests infDC dictate the nature of the T cell response during LN flare. Targeting infDC or their associated T cell phenotype may attenuate renal inflammation and improve outcomes in LN.

Funding

  • Other NIH Support