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Resident macrophages reprogram toward a developmental state after acute kidney injury
- Source :
- JCI Insight. 4
- Publication Year :
- 2019
- Publisher :
- American Society for Clinical Investigation, 2019.
-
Abstract
- Acute kidney injury (AKI) is a devastating clinical condition affecting at least two-thirds of critically ill patients, and, among these patients, it is associated with a greater than 60% risk of mortality. Kidney mononuclear phagocytes (MPs) are implicated in pathogenesis and healing in mouse models of AKI and, thus, have been the subject of investigation as potential targets for clinical intervention. We have determined that, after injury, F4/80(hi)-expressing kidney-resident macrophages (KRMs) are a distinct cellular subpopulation that does not differentiate from nonresident infiltrating MPs. However, if KRMs are depleted using polyinosinic/polycytidylic acid (poly I:C), they can be reconstituted from bone marrow–derived precursors. Further, KRMs lack major histocompatibility complex class II (MHCII) expression before P7 but upregulate it over the next 14 days. This MHCII(–) KRM phenotype reappears after injury. RNA sequencing shows that injury causes transcriptional reprogramming of KRMs such that they more closely resemble that found at P7. KRMs after injury are also enriched in Wingless-type MMTV integration site family (Wnt) signaling, indicating that a pathway vital for mouse and human kidney development is active. These data indicate that mechanisms involved in kidney development may be functioning after injury in KRMs.
- Subjects :
- 0301 basic medicine
Nephrology
medicine.medical_specialty
Kidney
Innate immune system
business.industry
Wnt signaling pathway
Acute kidney injury
Kidney development
General Medicine
medicine.disease
Pathogenesis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Downregulation and upregulation
030220 oncology & carcinogenesis
Internal medicine
Immunology
Medicine
business
Research Article
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....5572a9d3ab2e4a284c53c076fb89ed22