Innate Immune Cells Are Regulated by Axl in Hypertensive Kidney.

Area of Science:

• Immunology
• Nephrology
• Hypertension Research

Background:

• The interplay between innate and adaptive immunity in kidney damage during salt-dependent hypertension remains poorly understood.
• Investigating the role of innate immune responses is crucial for understanding early hypertensive kidney dysfunction.

Purpose of the Study:

• To investigate the role of the receptor tyrosine kinase Axl in the innate immune response within the hypertensive kidney.
• To determine the impact of Axl on early renal dysfunction in a mouse model of salt-dependent hypertension with lymphocyte deficiency.

Main Methods:

• Utilized lymphocyte-deficient (Rag1-/-) mice to isolate the innate immune response.
• Generated global Axl knockout mice on a Rag1-/- background and chimeric mice with Axl deficiency in innate immune cells.
• Conducted bioinformatics analyses of Axl-related gene-gene interaction networks.
• Investigated the role of complement C3 in Axl-mediated cell interactions.

Main Results:

• Increased CD11b+ myeloid cells in the kidney medulla correlated with salt/water retention and hypertension in Rag1-/- mice.
• Global deletion of Axl in Rag1-/- mice reversed kidney dysfunction and myeloid cell accumulation.
• Axl deficiency in innate immune cells significantly improved kidney function and abolished early hypertension.
• Complement C3 was identified as important for Axl-mediated myeloid and vascular cell interactions.

Conclusions:

• Innate immunity plays a critical role in renal dysfunction during early stages of hypertension.
• The receptor tyrosine kinase Axl significantly influences innate immune responses in the hypertensive kidney.
• Targeting Axl in innate immune cells presents a potential therapeutic strategy for early hypertension-related kidney damage.