Background/Purpose: We have recently identified inflammatory dendritic cells (InfDC) in human lupus kidneys. These cells are over expressed in LN patients compared to healthy controls. Knowledge on how the infDC interact with intra-renal T cells and their role in pathogenesis of LN kidney is crucially needed

Methods: We examined infDC and T cells in the kidneys of NZM 2410 (NZM), from proteinuric (prot-NZM) mice (proteinuria ≥300mg/dl) and pre-proteinuric NZM (pre-prot-NZM) mice by Immunofluorescence (IF). To quantitatively assess infDC and various T cells, we analyzed single cell suspensions obtained by enzymatic digestion followed by gentle MACS dissociation from prot-NZM kidneys and pre-prot-NZM kidneys by multi-color flow cytometry using specific markers for infDC and T cells

Results: The immunofluorescence (IF) studies recapitulated the human LN robust infiltration of the infDC marked by FcRγ in the periglomerular and tubulointerstitium in prot-NZM compared to pre-prot-NZM. The infDC were also identified to be in close proximity to CD3+ T cells constant with an immunological synape. Further characterization by IF revealed infDC in mice LN were FcRγ⁺, MHCII⁺,CD11c⁺,CD163^–,CD11b⁺,Ly6C⁺. Interestingly, 2 subtypes of infDC were identified in NZM mice, FcRγ⁺MHCII⁺CD11c⁺,CD11b⁺ and FcRγ⁺MHCII⁺CD11c^–,CD11b⁺ and differentiated by the presence or absence of CD11c. Flow cytometry analysis of T helper cell phenotypes shows that Th17 expression, but not Th1 was upregulated significantly in prot-NZM compared to pre-prot-NZM in parallel to infDC.

Conclusion: 1) Similar to human LN, infDC are abundant in prot-NZM LN kidneys compared to respective pre-prot NZM and healthy control kidneys; 2) infDC synapse with CD3+ T cells in LN kidneys; and 3) Th17 cells, but not Th1 cells, correlate with infDC’s expression in LN kidneys. These data suggests that infDC regulate the intra-renal Th17 cell response in LN and contribute to IL-17 mediated kidney injury. Ongoing studies will examine if these infDC are necessary or sufficient to cause LN.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/inflammatory-dendritic-cell-and-th17-polarization-in-mouse-model-of-lupus-nephritis/