Effects Of Kiss-1 Receptor Gpr54 On T-cell Development And Immune Functions

Gpr54 and its ligand Kiss1 have been recognized as versatile genes that can regulate cancer, hormones, energy metabolism, and many other functions. Under physiological circumstances, Gpr54/Kissl can regulate mammalian gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, promote the normal start of puberty. As we all know, thymus associated with hormones and puberty, so we want to know if Gpr54 is involved in the regulation of thymus development.To investigate the effect of Gpr54/Kissl on thymus T cell development, we analyzed thymus and thymocytes in Gpr54 knockout mice. Results showed that, Gpr54 knockout mice had significantly increased thymus size and cell quantity. Also, there were changes in the histological structure of thymus, such as a much thinner cortex layer. In addition, Gpr54 knockout mice seemed has greater susceptibility to autoimmune disease, as in the experimental autoimmune encephalomyelitis (EAE) models, Gpr54 knockout mice exhibited a severer clinical symptoms.In order to minimize the impact of hormones and explore the direct role of Gpr54 on the regulation of T cell development, we next used pre-pubertal mice and castrated mice in further investigation. Before puberty, thymus of Gpr54 knockout mice showed no significant increase, but thymocyte development was also affected. Flow cytometry analysis of thymocyte suspension showed apparent changes of CD4-CD8-double-negative as well as single positive populations. Also Gpr54 knockout mice had significantly decreased proportion of Treg cell, these changes in functional T-cell population may affect immune functions. As in non-castrated animals, castrated Gpr54 knockout mice exhibited higher clinical score and inflammation. In addition, we found that T-cell proliferation was affected by Gpr54 defects under a variety of stimulations.In summary, Gpr54 has a direct regulatory role in T-cell development and maturation, and can affect the balance of T cell subsets. Gpr54 defects disrupt T-cell function and increase the animal’s susceptibility to autoimmune diseases.