RENAL CD141+ DENDRITIC CELLS INFILTRATION IN CRESCENTIC GLOMERULONEPHRITIS IN HUMAN AND MICE

T CHEN1, 2, Q CAO1, 2, R WANG1, P RAO1, 2, G ZHENG1, 2, Y WANG1, 2, DC HARRIS1, 2

1The Westmead Institute for Medical Research, Westmead, NSW; 2University of Sydney, Camperdown, NSW.

Aim: To investigate the correlation between CD141+ dendritic cell (DC) infiltration and clinicopathologic features in human crescentic glomerulonephritis (GN) and to investigate possible underlying mechanisms of injury in a murine model.

Background: CD141+ DCs have recently been identified as a unique myeloid DC subset that plays a significant role in immune regulation. These DCs have been shown to play an important role in murine crescentic GN. However, expression of CD141+ DC in human crescentic GN is unknown. .

Methods: Adult patients with a sole diagnosis of crescentic GN were enrolled in the study. Patients were excluded if they received immunosuppressant therapy before renal biopsy.

Anti-GBM disease was induced in C57BL/6 mice by injection of nephritic serum. Mice were examined at week 1 and week 3.

Results: In normal human kidney, CD141+DC were rarely present. However, the number significantly increased in patients with crescentic GN (P=0.021). Higher CD141+ DC density was associated with worse serum creatinine (P=0.029) and proteinuria (P=0.038). In contrast to previous studies, which showed myeloid DCs were mainly present in the interstitium, we also found a high number of CD141+ DCs in glomeruli. Similar to humans, we found CD103+ DCs (the murine equivalent of human CD141+ DCs) constituted only 2% of total leucocytes in normal murine kidneys. In murine anti-GBM disease, the number and proportion of kidney CD103+ DCs was significantly increased (P=0.021). CD103+ DCs were mainly present in the interstitium. We are examining pathological correlations and pathogenic mechanisms of CD 103+ DCs in this model.

Conclusions: Our data suggest that CD141+ DCs may play an important role in crescentic GN.

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The ASM is hosted by Australian and New Zealand Society of Nephrology.

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