Conventional Type 1 Dendritic Cells (cDC1) in Human Kidney Diseases: Clinico-Pathological Correlations

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 May 31

PMID 34054804

Citations 5

Authors

Titi Chen

Qi Cao

Ruifeng Wang

Guoping Zheng

Farhana Azmi

Jeffery Wang

Vincent W Lee

Yuan Min Wang

Hong Yu

Manish Patel

Chow Heok Png

Stephen I Alexander

Natasha M Rogers

Yiping Wang

David C H Harris

Affiliations

Soon will be listed here.

Abstract

Background: cDC1 is a subset of conventional DCs, whose most recognized function is cross-presentation to CD8 T cells. We conducted this study to investigate the number and location of cDC1s in various human kidney diseases as well as their correlation with clinico-pathological features and CD8 T cells.

Methods: We analyzed 135 kidney biopsies samples. Kidney diseases included: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), proliferative glomerulonephritis (GN) (IgA nephropathy, lupus nephritis, pauci-immune GN, anti-GBM disease), non-proliferative GN (minimal change disease, membranous nephropathy) and diabetic nephropathy. Indirect immunofluorescence staining was used to quantify cDC1s, CD1c DCs, and CD8 T cells.

Results: cDC1s were rarely present in normal kidneys. Their number increased significantly in ATN and proliferative GN, proportionally much more than CD1c DCs. cDC1s were mainly found in the interstitium, except in lupus nephritis, pauci-immune GN and anti-GBM disease, where they were prominent in glomeruli and peri-glomerular regions. The number of cDC1s correlated with disease severity in ATN, number of crescents in pauci-immune GN, interstitial fibrosis in IgA nephropathy and lupus nephritis, as well as prognosis in IgA nephropathy. The number of CD8 T cells also increased significantly in these conditions and cDC1 number correlated with CD8 T cell number in lupus nephritis and pauci-immune GN, with many of them closely co-localized.

Conclusions: cDC1 number correlated with various clinic-pathological features and prognosis reflecting a possible role in these conditions. Their association with CD8 T cells suggests a combined mechanism in keeping with the results in animal models.

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References

Aasarod K, Bostad L, Hammerstrom J, Jorstad S, Iversen B . Wegener's granulomatosis: inflammatory cells and markers of repair and fibrosis in renal biopsies--a clinicopathological study. Scand J Urol Nephrol. 2002; 35(5):401-10. DOI: 10.1080/003655901753224477. View

Chang J, Eggenhuizen P, OSullivan K, Alikhan M, Holdsworth S, Ooi J . CD8+ T Cells Effect Glomerular Injury in Experimental Anti-Myeloperoxidase GN. J Am Soc Nephrol. 2016; 28(1):47-55. PMC: 5198281. DOI: 10.1681/ASN.2015121356. View

Dolff S, Abdulahad W, Arends S, van Dijk M, Limburg P, Kallenberg C . Urinary CD8+ T-cell counts discriminate between active and inactive lupus nephritis. Arthritis Res Ther. 2013; 15(1):R36. PMC: 3672789. DOI: 10.1186/ar4189. View

Segerer S, Heller F, Lindenmeyer M, Schmid H, Cohen C, Draganovici D . Compartment specific expression of dendritic cell markers in human glomerulonephritis. Kidney Int. 2008; 74(1):37-46. DOI: 10.1038/ki.2008.99. View

Villani A, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J . Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science. 2017; 356(6335). PMC: 5775029. DOI: 10.1126/science.aah4573. View

Wilde B, van Paassen P, Damoiseaux J, Heerings-Rewinkel P, van Rie H, Witzke O . Dendritic cells in renal biopsies of patients with ANCA-associated vasculitis. Nephrol Dial Transplant. 2009; 24(7):2151-6. DOI: 10.1093/ndt/gfp019. View

Daniil Z, Kitsanta P, Kapotsis G, Mathioudaki M, Kollintza A, Karatza M . CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis. Respir Res. 2005; 6:81. PMC: 1199622. DOI: 10.1186/1465-9921-6-81. View

Zickert A, Oke V, Parodis I, Svenungsson E, Sundstrom Y, Gunnarsson I . Interferon (IFN)-λ is a potential mediator in lupus nephritis. Lupus Sci Med. 2016; 3(1):e000170. PMC: 5133405. DOI: 10.1136/lupus-2016-000170. View

van Es L, de Heer E, Vleming L, van der Wal A, Mallat M, Bajema I . GMP-17-positive T-lymphocytes in renal tubules predict progression in early stages of IgA nephropathy. Kidney Int. 2008; 73(12):1426-33. DOI: 10.1038/ki.2008.66. View

10.

Guilliams M, Dutertre C, Scott C, McGovern N, Sichien D, Chakarov S . Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species. Immunity. 2016; 45(3):669-684. PMC: 5040826. DOI: 10.1016/j.immuni.2016.08.015. View

11.

Arazi A, Rao D, Berthier C, Davidson A, Liu Y, Hoover P . The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019; 20(7):902-914. PMC: 6726437. DOI: 10.1038/s41590-019-0398-x. View

12.

Lech M, Avila-Ferrufino A, Allam R, Segerer S, Khandoga A, Krombach F . Resident dendritic cells prevent postischemic acute renal failure by help of single Ig IL-1 receptor-related protein. J Immunol. 2009; 183(6):4109-18. DOI: 10.4049/jimmunol.0900118. View

13.

Weidner S, Carl M, Riess R, Rupprecht H . Histologic analysis of renal leukocyte infiltration in antineutrophil cytoplasmic antibody-associated vasculitis: importance of monocyte and neutrophil infiltration in tissue damage. Arthritis Rheum. 2004; 50(11):3651-7. DOI: 10.1002/art.20607. View

14.

Almaani S, Meara A, Rovin B . Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2016; 12(5):825-835. PMC: 5477208. DOI: 10.2215/CJN.05780616. View

15.

Dolff S, Abdulahad W, van Dijk M, Limburg P, Kallenberg C, Bijl M . Urinary T cells in active lupus nephritis show an effector memory phenotype. Ann Rheum Dis. 2010; 69(11):2034-41. DOI: 10.1136/ard.2009.124636. View

16.

Fiore N, Castellano G, Blasi A, Capobianco C, Loverre A, Montinaro V . Immature myeloid and plasmacytoid dendritic cells infiltrate renal tubulointerstitium in patients with lupus nephritis. Mol Immunol. 2007; 45(1):259-65. DOI: 10.1016/j.molimm.2007.04.029. View

17.

Brodeur T, Robidoux T, Weinstein J, Craft J, Swain S, Marshak-Rothstein A . IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells. J Immunol. 2015; 195(11):5251-60. PMC: 4655158. DOI: 10.4049/jimmunol.1500777. View

18.

OSullivan K, Lo C, Summers S, Elgass K, McMillan P, Longano A . Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Kidney Int. 2015; 88(5):1030-46. DOI: 10.1038/ki.2015.202. View

19.

Bagavant H, Fu S . Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol. 2009; 21(5):489-94. PMC: 2841319. DOI: 10.1097/BOR.0b013e32832efff1. View

20.

Ysebaert D, De Greef K, Vercauteren S, Ghielli M, Verpooten G, Eyskens E . Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrol Dial Transplant. 2000; 15(10):1562-74. DOI: 10.1093/ndt/15.10.1562. View