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Published on: November 15, 2024
The Th17-defining transcription factor RORγt promotes glomerulonephritis
Oliver M Steinmetz1, Shaun A Summers, Poh-Yi Gan
1Centre for Inflammatory Diseases, Monash University Department of Medicine, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Journal of the American Society of Nephrology : JASN
|December 25, 2010
Summary
The transcription factor RORγt drives the development of crescentic glomerulonephritis by promoting T helper 17 (Th17) cell responses. Mice lacking RORγt show protection from this kidney disease, indicating RORγt as a key factor.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Th17 cell responses are implicated in glomerulonephritis pathogenesis.
- The role of the key Th17 transcription factor, RORγt, in glomerulonephritis remains unclear.
Purpose of the Study:
- To investigate whether RORγt promotes the development of crescentic glomerulonephritis.
- To elucidate the specific role of RORγt in nephritogenic Th17 responses.
Main Methods:
- Induction of crescentic glomerulonephritis in wild-type and RORγt-deficient mice.
- Cell-transfer studies using RORγt-deficient splenocytes and CD4+ T cells into Rag1(-/-) mice.
- Analysis of renal histology, function, and leukocyte infiltration.
Main Results:
- RORγt-deficient mice were protected from glomerulonephritis, exhibiting reduced injury and leukocyte infiltration.
- Cell-transfer studies confirmed that RORγt-expressing T cells drive severe glomerulonephritis.
- RORγt deficiency in T helper cells, even when regulatory T cells were depleted, protected against disease development.
Conclusions:
- RORγt is a critical promoter of crescentic glomerulonephritis.
- RORγt drives glomerulonephritis by directing nephritogenic Th17 responses.
- Targeting RORγt may offer a therapeutic strategy for glomerulonephritis.
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