Publications

Prostaglandin E2 (PGE2) promotes Th17 expansion while otherwise inhibiting other CD4+ T cell subsets. Here, we identified a PGE2-dependent pathway that induces pathogenic Th17 cells in autoimmune disease and is regulated by the transcription factor RORC. Compared with other CD4+ cell types from healthy subjects, there is a surprising lack of the prostaglandin receptor EP2 on Th17 cells; therefore, we examined the hypothesis that RORγt, which is highly expressed in Th17 cells, mediates EP2 downregulation. Chromatin immunoprecipitation followed by DNA sequencing revealed that RORγt binds directly to Ptger2 (the gene encoding EP2 receptor) in Th17 cells isolated from WT mice. In Th17 cells isolated from humans, RORC repressed EP2 by directly silencing PTGER2 transcription, and knock down of RORC restored EP2 expression in Th17 cells. Compared with Th17 cells from healthy individuals, Th17 cells from patients with MS exhibited reduced RORC binding to the PTGER2 promoter region, resulting in higher EP2 levels and increased expression of IFN-γ and GM-CSF. Finally, overexpression of EP2 in Th17 cells from healthy individuals induced a specific program of inflammatory gene transcription that produced a pathogenic Th17 cell phenotype. These findings reveal that RORC directly regulates the effects of PGE2 on Th17 cells, and dysfunction of this pathway induces a pathogenic Th17 cell phenotype.

Global health has become an increasingly prominent component of foreign policy in the last decade. The term health diplomacy has been used to describe this growing interface between foreign policy and global health, and it encompasses both the concept of using health to further foreign policy objectives as well as the idea that diplomatic tools can be helpful for attaining public health goals. The Chinese presence in Africa has grown in the last 15 years, generating increased interest in Sino-African relations. While much has been written in recent years about the Chinese presence in Africa, the growing numbers of Africans in China have attracted considerably less attention. Many are small-scale traders and might be expected to face many of the health challenges common among foreign migrants, but their health needs have been largely unrecognised. In this paper, we consider how a health diplomacy approach could be applied to African migrants in China, and the potential advantages and limitations of this strategy. We identify areas of overlap between public health, trade and foreign policy goals that can be emphasised to generate support for improved services for African migrants in China and to engage partners from a diversity of sectors.