Immune cells during compensatory renal hypertrophy after unilateral nephrectomy

Area of Science:

• Nephrology
• Immunology
• Renal Physiology

Background:

• Compensatory renal hypertrophy (CRH) after unilateral nephrectomy (UNx) is crucial for kidney function but its mechanisms are complex.
• Understanding immune cell roles in CRH is vital for kidney donor management and post-nephrectomy recovery.

Purpose of the Study:

• To investigate the dynamic changes and roles of immune cells during compensatory renal hypertrophy (CRH) following unilateral nephrectomy (UNx) in a mouse model.
• To explore the specific contributions of innate and adaptive immune cells to kidney function recovery and glomerular filtration rate (GFR) changes post-UNx.

Main Methods:

• Unilateral nephrectomy (UNx) performed on wild-type (WT) mice, with glomerular filtration rate (GFR) measurements, flow cytometry, and single-cell RNA sequencing over 8 weeks.
• Utilized Rag1 knockout (Rag1-/-) mice to assess the impact of adaptive immunity on GFR during CRH.
• Analyzed immune cell populations, including neutrophils, macrophages, NK cells, and various T cell subsets (CD4+, CD8+, DN-T), along with immune checkpoint molecule expression (PD-1, CTLA-4, TIGIT).

Main Results:

• Dynamic, time-dependent immune cell alterations observed post-UNx, with rapid innate immune cell (neutrophils, macrophages) increases and initial NK cell decrease.
• Adaptive immune cells (CD4+, CD8+, DN-T cells) exhibited changes in resident (CD69) and regulatory markers (CD4+CD25+), alongside dynamic expression of immune checkpoints (PD-1, CTLA-4, TIGIT).
• Rag1-/- mice showed significantly higher GFR in the later recovery phase compared to WT mice, suggesting a role for adaptive immunity in modulating GFR during CRH.

Conclusions:

• CRH involves a multi-phase immune response characterized by early innate immune activation and subsequent adaptive immune regulation.
• Immune cell dynamics, including shifts in immune checkpoints, significantly influence compensatory kidney changes and GFR recovery post-UNx.
• Findings provide insights into the immune mechanisms governing kidney adaptation after UNx, relevant to living kidney donors and other clinical scenarios.