Renal CD64+ MPs protect kidney in both cisplatin and ischemia reperfusion induced acute kidney injury

Ji, Xingqi (2023): Renal CD64+ MPs protect kidney in both cisplatin and ischemia reperfusion induced acute kidney injury. Dissertation, LMU München: Medizinische Fakultät

Abstract

Mononuclear phagocytes (MPs) consist of dendritic cells (DCs), macrophages and monocytes, they have important functions in mediating immune responses in tissues. It is reported in kidney contains diverse MP subsets, however, due to insufficient subset specific depletion model, the functions of these MPs are unclear in acute kidney injury (AKI). C-Type Lectin Domain Containing 9A (Clec9a) is a receptor sensing polymeric F-actin exposed in necrotic cells, and it is highly expressed on common dendritic cell progenitor (CDP) that give rise to dendritic cells (DCs), by genetic tracing of Clec9a expression histroy will specifically mark DCs but not other immune cells. In steady state the kidney contains at least 4 subsets with Clec9a expressing history, cDC1, cDC2 and a large CD64 expressing group which can be subdivided into F4/80hi and CD11bhi sub-populations. By using cDC1 depletion model (XCR1-venus-DTR), we found cDC1 depletion did not increase kidney injury severity after cisplatin treatment. The similar situation also happened when we depleted cDC2 in Clec9acreIRF4f/f mice treated with cisplatin. However, cisplatin induced injury increased significantly when we used newly generated Clec9acreCD64iDTR model to deplete CD64+ MPs in the kidney, this result indicated CD64+ MPs can protect kidney in cisplatin induced AKI. By constructing ischemia reperfusion acute kidney injury, we found CD64+ MPs also have protective role in both steady state and inflammation state, the mechanism could be attributed to regulation of anti/pro-inflammatory cytokines produced by CD64+ MPs. Thus, we conclude CD64+ MPs protect kidney both in cisplatin induced AKI and also in ischemia reperfusion induced AKI, which may shed lights to therapeutic targeting of this population for curing AKI in the future.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 26. Oktober 2023
• 1. Bericht­erstatter:in: Schraml-Schotta, Barbara