Abstract
GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system. However, flow cytometry revealed a significant reduction in the peripheral regulatory T cell population and a moderate decrease in CD4 single-positive thymocytes in prepubertal Gpr54−/− mice. These phenotypes were confirmed in chimeric mice with GPR54 deficient bone marrow-derived cells. In addition, we found elevated T cell activation in peripheral and thymic T cells in Gpr54−/− mice. When intact mice were immunized with myelin oligodendrocyte glycoprotein, a more severe experimental autoimmune encephalomyelitis (EAE) developed in the Gpr54−/− mice. Interestingly, aggravated EAE disease was also manifested in castrated and bone marrow chimeric Gpr54−/− mice compared to the respective wild-type control, suggesting a defect in self-tolerance resulting from GPR54 deletion through a mechanism that bypassed sex hormones. These findings demonstrate a novel role for GPR54 in regulating self-tolerant immunity in a sex hormone independent manner.
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Acknowledgements
We are grateful to Dr. Eric L. Gustafson at Schering-Plough Research Institute for providing the male and female Gpr54+/− mouse line. This work was supported by the National Natural Science Foundation of China (31271468) and the Science and Technology Commission of Shanghai Municipality (12ZR1408700).
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Xing, R., Liu, F., Yang, Y. et al. GPR54 deficiency reduces the Treg population and aggravates experimental autoimmune encephalomyelitis in mice. Sci. China Life Sci. 61, 675–687 (2018). https://doi.org/10.1007/s11427-017-9269-8
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DOI: https://doi.org/10.1007/s11427-017-9269-8