Melanocortin 1 receptor alleviates collagen-induced arthritis by upregulating T helper 1/T helper 17 cells and downregulating regulatory T cells.

Objective: Arthritis is a common chronic disease. The T cell subpopulation, as a key element in the immune system, plays a crucial role in arthritis. This work aimed to explore the involvement of melanocortin 1 receptor (MC1R) in collagen-induced arthritis (CIA) and how it affects the balance of proinflammatory and anti-inflammatory T cell subsets. Material and Methods: Using flow cytometry, the ratios of T helper (Th)1, Th17, and regulatory T (Treg) cells were examined. Using the enzyme-linked immunosorbent assay, pro-interleukin (IL)-17, interferon (IFN)-g, anti-IL-10, and IL-4 were measured. Results: MC1R knockout (MC1R-KO) mice exhibited an increase in the proportion of Th1 and Th17 cells compared with wild-type mice. The proportion of Treg cells in MC1R-KO mice was reduced. The levels of IL-17 and IFN-g in MC1R-KO mice increased, whereas those of IL-10 and IL-4 decreased. Conclusion: MC1R-KO mice exacerbated CIA by upregulating the numbers of Th1 and Th17 cells and decreasing the proportion of Treg cells. The increased production of IL-17 and IFN-g, along with the reduced IL-10 and IL-4 levels, further contributed to the enhanced inflammatory response. These findings suggest that MC1R plays a crucial role in the regulation of immune responses and inflammation in CIA. Targeting MC1R may have therapeutic potential for autoimmune diseases characterized by dysregulated T cell subsets.