Dataset Information

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties.

ABSTRACT:

Background

Mononuclear phagocytes (MPs), including macrophages, monocytes, and dendritic cells (DCs), are phagocytic cells with important roles in immunity. The developmental origin of kidney DCs has been highly debated because of the large phenotypic overlap between macrophages and DCs in this tissue.

Methods

We used fate mapping, RNA sequencing, flow cytometry, confocal microscopy, and histo-cytometry to assess the origin and phenotypic and functional properties of renal DCs in healthy kidney and of DCs after cisplatin and ischemia reperfusion-induced kidney injury.

Results

Adult kidney contains at least four subsets of MPs with prominent Clec9a-expression history indicating a DC origin. We demonstrate that these populations are phenotypically, functionally, and transcriptionally distinct from each other. We also show these kidney MPs exhibit unique age-dependent developmental heterogeneity. Kidneys from newborn mice contain a prominent population of embryonic-derived MHCII^negF4/80^hiCD11b^low macrophages that express T cell Ig and mucin domain containing 4 (TIM-4) and MER receptor tyrosine kinase (MERTK). These macrophages are replaced within a few weeks after birth by phenotypically similar cells that express MHCII but lack TIM-4 and MERTK. MHCII⁺F4/80^hi cells exhibit prominent Clec9a-expression history in adulthood but not early life, indicating additional age-dependent developmental heterogeneity. In AKI, MHCII^negF4/80^hi cells reappear in adult kidneys as a result of MHCII downregulation by resident MHCII⁺F4/80^hi cells, possibly in response to prostaglandin E2 (PGE2). RNA sequencing further suggests MHCII⁺F4/80^hi cells help coordinate the recruitment of inflammatory cells during renal injury.

Conclusions

Distinct developmental programs contribute to renal DC and macrophage populations throughout life, which could have important implications for therapies targeting these cells.

SUBMITTER: Salei N

PROVIDER: S-EPMC7003301 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties.

Salei Natallia N Rambichler Stephan S Salvermoser Johanna J Papaioannou Nikos E NE Schuchert Ronja R Pakalniškytė Dalia D Li Na N Marschner Julian A JA Lichtnekert Julia J Stremmel Christopher C Cernilogar Filippo M FM Salvermoser Melanie M Walzog Barbara B Straub Tobias T Schotta Gunnar G Anders Hans-Joachim HJ Schulz Christian C Schraml Barbara U BU

Journal of the American Society of Nephrology : JASN 20200113 2

<h4>Background</h4>Mononuclear phagocytes (MPs), including macrophages, monocytes, and dendritic cells (DCs), are phagocytic cells with important roles in immunity. The developmental origin of kidney DCs has been highly debated because of the large phenotypic overlap between macrophages and DCs in this tissue.<h4>Methods</h4>We used fate mapping, RNA sequencing, flow cytometry, confocal microscopy, and histo-cytometry to assess the origin and phenotypic and functional properties of renal DCs in ...[more]

PMID: 31932472

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Project description:There is mounting evidence that galectin-3 is a prognostic and diagnostic biomarker associated with diverse diseases and conditions, including cancer, cardiovascular disease, autoimmunity, wound healing, allergic disease, and chronic inflammation in general. Yet, whether and exactly how galectin-3 may participate in the pathogenesis of these diseases remains poorly understood. Recently, we have linked the expression of galectin-3 on the A549 epithelial cell line -an adenocarcinoma, to the activation of human basophils for the release of histamine and secretion of IL-4 and IL-13. These responses proved dependent on cell-to-cell contact, basophil expression of IgE, were inhibited by n-acetyllactosamine, and were ablated when basophils were co-cultured with A549 clones lacking galectin-3 expression. While recombinant galectin-3 failed to activate basophils when in solution, microspheres expressing this lectin did so by mimicking the responses seen when using A549 cells. Given the IgE dependency of the basophil responses, and the fact that galectin-3 is long known to bind this immunoglobulin, we hypothesize that a similar mode of activation extends to other IgE-bearing cells. To investigate this possibility, we tested epithelial cell-associated galectin-3 for its capacity to activate human dendritic cells, including the plasmacytoid and myeloid subtypes as well as monocytes, all of which bind IgE. Indeed, results indicate that epithelial cell-associated galectin-3 activated these cells for robust production of TNF-α and IL-6 and up-regulated the expression of activation markers found on dendritic cells. Moreover, many of the same parameters previously observed for basophils applied to the findings herein, including evidence that matrix-bound galectin-3 (whether on epithelial cells or microspheres) facilitates this mode of activation. In contrast, IgE expression was dispensable for these galectin-3-dependent cytokine responses, implying that this lectin activates dendritic cells (and monocytes) by binding to a glycoprotein other than this immunoglobulin. Overall, these findings further demonstrate how galectin-3 mediates immune cell activation, providing novel insight into how this lectin may promote chronic inflammation underlying the pathogenesis of many diseases.

Dataset Information

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties.

Background

Methods

Results

Conclusions

Publications

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties.

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