The University of Toledo Translation Journal of Medical Sciences 
Nephrology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 5; 11(1):e1-e1 

MC1R Deficiency Enhances Th1 Response 
and Impairs Regulatory T Cell Homeostasis 
In Nephrotoxic Serum Nephritis 
Bohan Chen1*, Xuejing Guan1, Yan Ge1, Lance Dworkin1, Rujun Gong1 

1Division of Nephrology, Department of Medicine, The University of Toledo, 
Toledo, OH 43614 

*Corresponding author: Lance.dworkin@utoledo.edu

Published: 05 May 2023 

Background: The melanocortin neuropeptides, represented by adrenocorticotropic hormone, have 
recently emerged as a novel therapeutic choice for treating refractory glomerular diseases. As a key 
cognate receptor of the melanocortin hormone system, melanocortin 1 receptor (MC1R) plays a pivotal 
role in regulating immune response and inflammation, and has become a novel therapeutic target for a 
number of diseases. However, its role in the pathogenesis of immune-mediated glomerular disease 
remains unknown.   

Methods: Wild-type (WT) mice and the recessive yellow mice (e/e) with the naturally occurring loss-of-
function null mutation of MC1R received injection of the rabbit anti-mouse nephrotoxic serum (NTS) to 
develop the NTS nephritis and were examined 2 weeks later.   

Results: The e/e mice developed more severe crescentic glomerulonephritis than WT mice, marked by 
aggravated proteinuria, kidney dysfunction, and renal lesions like glomerular hypercellularity, crescent 
formation, and renal inflammation and fibrosis. The exacerbated NTS nephritis in e/e mice was 
associated with greater levels of autologous IgG2c and IgG3 either deposited in glomeruli or in sera. In 
addition, profiling of signature cytokines of Th immunity revealed that e/e mice with NTS nephritis 
exhibited higher renal expression of IFN-γ, and an increasing trend in renal expression of TNF-α, as 
compared with WT mice, consistent with a reinforced Th1 immune response. Moreover, shown by 
immunohistochemistry staining, the number of FoxP3+ regulatory T cells in the NTS nephritic kidneys 
was diminished in e/e mice, as compared with WT mice. Mechanistically, MC1R was evidently detected 
in diverse renal leukocytes prepared from the diseased WT mice, including T lymphocytes, suggesting 
that T cells may be direct effector cells of the melanocortin hormones via MC1R signaling.    

Conclusion: MC1R-mediated melanocortinergic signaling represses Th1 immune response and is 
required for regulatory T cell homeostasis in murine models of NTS nephritis, resulting in renal 
protection in experimental crescentic glomerulonephritis. 

https://dx.doi.org/10.46570/utjms.vol11-2023-763 

https://dx.doi.org/10.46570/utjms.vol11-2023-763
mailto:Lance.dworkin@utoledo.edu