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The immunoregulatory roles of non-haematopoietic cells in the kidney

Nature Reviews Nephrology volume 20, pages 206–217 (2024)Cite this article

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An Author Correction to this article was published on 23 November 2023

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Abstract

The deposition of immune complexes, activation of complement and infiltration of the kidney by cells of the adaptive and innate immune systems have long been considered responsible for the induction of kidney damage in autoimmune, alloimmune and other inflammatory kidney diseases. However, emerging findings have highlighted the contribution of resident immune cells and of immune molecules expressed by kidney-resident parenchymal cells to disease processes. Several types of kidney parenchymal cells seem to express a variety of immune molecules with a distinct topographic distribution, which may reflect the exposure of these cells to different pathogenic threats or microenvironments. A growing body of literature suggests that these cells can stimulate the infiltration of immune cells that provide protection against infections or contribute to inflammation — a process that is also regulated by draining kidney lymph nodes. Moreover, components of the immune system, such as autoantibodies, cytokines and immune cells, can influence the metabolic profile of kidney parenchymal cells in the kidney, highlighting the importance of crosstalk in pathogenic processes. The development of targeted nanomedicine approaches that modulate the immune response or control inflammation and damage directly within the kidney has the potential to eliminate the need for systemically acting drugs.

Key points

  • Non-myeloid kidney parenchymal cells (KPCs) express molecules that are shared with immune cells; the expression of these molecules may have distinct topological associations and may increase in response to inflammation.

  • Kidney injury can induce the infiltration of immune cells; these cells may have protective or pro-inflammatory features depending on the phase of the disease process. In addition, kidney-resident immune cells may have a surveillance or regulatory role in the kidney but can accumulate in response to injury.

  • Components of the immune system, such as autoantibodies, cytokines and immune cells, can influence the metabolic profile of KPCs in the kidney.

  • Conversely, KPCs can contribute to inflammation by providing metabolites or through the secretion of chemokines and cytokines.

  • The cortex and the medulla of kidney tissue can contain distinct types of tertiary lymphoid organs, which may possess pathogenic or regulatory properties.

  • Targeted delivery of drugs to KPCs holds promise for preventing or reversing the inflammatory response in specific forms of kidney injury and disease.

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Fig. 1: Soluble and cellular mediators of inflammation in the kidney.
Fig. 2: Immune features of kidney parenchymal cells.
Fig. 3: Lymphoid organs in kidney disease.
Fig. 4: Intercellular crosstalk within the kidneys between resident and infiltrating cells.

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Authors and Affiliations

  1. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    George C. Tsokos, Afroditi Boulougoura, Yushiro Endo & Hao Li

  2. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Vivek Kasinath & Reza Abdi

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All authors researched data for the article, contributed substantially to discussion of the content and wrote the article. G.C.T., A.B., Y.E., R.A. and H.L reviewed and/or edited the manuscript before submission.

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Tsokos, G.C., Boulougoura, A., Kasinath, V. et al. The immunoregulatory roles of non-haematopoietic cells in the kidney. Nat Rev Nephrol 20, 206–217 (2024). https://doi.org/10.1038/s41581-023-00786-x

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