Immune complexes and complexity: investigating mechanisms of renal disease

Abstract

The deposition of immune complexes is the causal factor in distinct renal pathologies, e.g., lupus nephritis and membranous nephritis. The location of these deposits within a tissue biopsy is often the key to establishing a diagnosis. However, how immune complexes come to be deposited below the vascular endothelium was, until now, a mystery, as was their contribution to inducing inflammation. A recent paper in Cell by Stamatiades et al. (Cell 164(4):991–1003, 2016) demonstrates the active transport of immune complexes by the vascular endothelial cells and an Fc receptor-dependent uptake by tissue-resident macrophages. This leads to the activation of these macrophages and the release of pro-inflammatory cytokines, which in turn recruits immune cells from the blood into the kidney. The identification of these mechanisms should lead to a better stratification of kidney diseases and hopefully to the development of specific therapies.

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Abbreviations

AIM:

Apoptosis inhibitor of macrophage protein

APC:

Antigen-presenting cell

CR:

Complement receptor

EM:

Electron microscopy

FcγR:

Fc gamma receptor

IgG:

Immunoglobulin γ chain

IgM:

Immunoglobulin µ chain

KALT:

Kidney-associated lymphoid tissue

pAPCs:

Professional antigen-presenting cells

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Acknowledgements

The authors are funded by DFG grants LI-1031/4-1 to JAL, and ME-1365/7-2, ME-1365/9-1, and SFB854 TP-A01 to PRM.

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Correspondence to Jonathan A. Lindquist.

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The authors declare no competing financial interests.

Ethical approval

All experiments were performed on tissue from euthanized animals in accordance with the German National Guidelines for the Use of Experimental Animals (Animal Protection Act, Tierschutzgesetz, TierSchG, in particular paragraphs 7 and 8). Animals were handled in accordance with the European Communities Council Directive 86/609/EEC. All possible efforts were made to minimize animal suffering and the number of animals used. This article does not contain any studies with human participants performed by any of the authors.

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Lindquist, J.A., Hildebrandt, J., Philipsen, L. et al. Immune complexes and complexity: investigating mechanisms of renal disease. Int Urol Nephrol 49, 735–739 (2017). https://doi.org/10.1007/s11255-016-1450-5

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Keywords

  • Kidney
  • Macrophages
  • Fc gamma receptors
  • Immune complexes
  • Inflammatory cell recruitment