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Abstract: TH-PO416

Expression of T Regulatory Cells in the Kidneys of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene-Knockout Mice

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Gogulamudi, Venkateswara R, Tulane University Health Sciences Center, School of Medicie, New Orleans, Louisiana, United States
  • Subramanian, Umadevi, Tulane University Health Sciences Center, School of Medicie, New Orleans, Louisiana, United States
  • Pandey, Kailash Nath, Tulane University Health Sciences Center, School of Medicie, New Orleans, Louisiana, United States
Background

Background: Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) disruption activates the pro-inflammatory responses in null mutant mice. There is increasing evidence that imbalanced immune responses play important role in physiological changes and complications of hypertension leading to organ damage. T Regulatory cells are defined as vital immune cellular population and they are likely to aid in immune tolerance by dampening the harmful effects of the other immune cellular population. The objective of our study was to elucidate the role of T regulatory cell markers and their expression levels in Npr1 gene-disrupted mice.

Methods

Methods: In the present study, 0-copy (Npr1-/-), 1-copy (Npr1+/-), and 2-copy (Npr1+/+) mice were pre-treated with rapamycin (2mg/kg/day) for 14 days. Spleen was collected, T cells were pre-enriched from spleen by using magnetic separation columns, and phenotypic expression of T regulatory subsets (Foxp3+, CD25+ and CD4+) were determined by flow cytometry.

Results

Results: The Npr1 gene-disrupted mice displayed the significant reduction of Foxp3+ expression in 0-copy (77.5%) and 1-copy (71.5%) mice compared with 2-copy wild-type mice. Similarly, CD25+ expression was reduced in 0-copy (75%) and in 1-copy (60%) mice compared with wild-type controls. In contrast, the total CD4+ count was potentially up-regulated by 40% in 0-copy and 31% in 1-copy mice compared with 2-copy control mice. Treatment with rapamycin showed a substantial increase of Foxp3+ cells by 17.38% (P<0.001) in 0-copy and 8.23 % (P<0.001) in 1-copy mice and CD25+ T cells by 62.2% (P<0.001) in 0-copy and 38.1 % (P<0.001) in 1-copy mice.

Conclusion

Conclusions: The present results demonstrate that plummeting levels of T regulatory cells in Npr1 gene-disrupted 0-copy and 1-copy mice provoke inflammatory responses in the kidney compared with wild-type mice. The treatment of 0-copy and 1-copy mice with rapamycin renders elevation of Tregs, suggesting the potential roles of Npr1 in down-regulation of pro- inflammatory renal immune conditions.

Funding

  • Other NIH Support