Inherited interstitial nephritis in kdkd mice

Area of Science:

• Immunology
• Nephrology
• Genetics

Background:

• kdkd mice develop progressive, autoimmune interstitial nephritis leading to renal failure.
• This T cell-mediated disease is inherited in an autosomal recessive manner and linked to mouse chromosome 10.
• The murine model closely resembles human medullary cystic disease, a condition not typically considered autoimmune.

Purpose of the Study:

• To investigate the immunological mechanisms underlying autoimmune interstitial nephritis in kdkd mice.
• To identify factors correlating with susceptibility to this autoimmune kidney disease.
• To explore potential therapeutic interventions for autoimmune nephritis.

Main Methods:

• Histological and immunological evaluation of kdkd mice.
• Analysis of T cell populations (CD8+, regulatory T cells) and their role in disease initiation.
• Assessment of disease inhibition through protein-calorie restriction, T cell infusions, and anti-ICAM-1 antibodies.

Main Results:

• Autoimmune nephritis is initiated by CD8+, H-2Kk-restricted T cells recognizing renal tubule antigens.
• Disease susceptibility correlates with the expression of regulatory T cells, not effector cells.
• Protein-calorie restriction, CBA/Ca CD8+ T cell infusions, and ICAM-1 blockade inhibit nephritis.

Conclusions:

• kdkd mice provide a valuable model for studying organ-specific autoimmunity and its resemblance to human medullary cystic disease.
• Understanding the genetic basis of this murine model and human disease can elucidate autoimmune mechanisms.
• Regulatory T cell dynamics play a crucial role in the susceptibility to autoimmune interstitial nephritis.