Chengcan Yao's lab studies the roles of bioactive lipids (eg prostaglandins) in modulation of immunity and inflammatory diseases.
Prostaglandins (PGs) are lipid mediators that are generated from arachidonic acid in response to various (physical, chemical or biological) stimuli, eg infection, inflammation and stress. PGs play essential roles in numerous physiological and pathological processes leading to body homeostasis or disease. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, which blocks biological synthesis of PGs, are widely used to treat acute as well as chronic inflammatory diseases such as pain, fever and arthritis. However, use of NSAIDs may also result in severe adverse effects, eg,gastrointestinal bleeding. Our group is investigating how PG signaling, especially in adaptive and innate immune cells, contributes to immune homeostasis and inflammatory responses, which could leading to successful strategies to pursue for future therapies against inflammatory disorders and to avoid adverse effects of NSAIDs.
A healthy gut houses trillions of commensal bacteria that significantly contribute to our health, eg helping us to digest food, develop immune system and stave off infections of invasive microorganisms. However, gut leakage of commensal bacteria into the circulatory system may trigger severe systemic inflammation. We have recently found that prostaglandin E2 (PGE2), the most well-known and important PG, constrains development of systemic inflammation through protecting against the gut epithelial damage. In the gut, PGE2 activates type 3 innate lymphoid cells (ILC3s) to maintain their homeostasis and promote their function, ie production of the reparative cytokine interleukin-22 (IL-22). IL-22 in turn contributes to the intestinal epithelial barrier function and impedes gut leakage of commensal bacteria [Duffin et al, Science 351,1333-1338 (2016)]. These findings provide valuable insight toward understanding how inactivation of cyclooxygenases may be harmful in severe bacterial infection and intestinal inflammation. Our findings also advance a crucial cellular and molecular mechanism for a scenario in which maintaining/augmenting PGE2 signaling protects against intestinal barrier injury and potentiates its repair.
CD4+ T cells play critical roles in autoimmune and inflammatory diseases. For example, interferon (IFN)-γ-producing Th1 and IL-17-producing Th17 cells are two main subsets of effector T cells that causes pathogenesis of autoimmunity and inflammation, while Foxp3-expressing regulatory T cells controls autoimmune and inflammatory responses. PGE2 has been long believed as an immunosuppressant in adaptive immune response, ie inhibiting T cell receptor signaling and inflammatory cytokine production. We have recently demonstrated that PGE2 promotes T cell-mediated autoimmune inflammation such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis and skin diseases. PGE2 promotes Th1 cell development/function through induction of IL-12 receptor via EP2/EP4-activated cAMP and PI3K. In addition, PGE2 also stimulates dendritic cells to produce IL-23 that further fosters Th17 cell proliferation [Yao et al, Nat Med 15, 633-640 (2009); Yao et al, Nat Commun.4, 1685 (2013)]. Our findings are supported by recent genome-wide association studies which suggested the association of PTGER4 (encoding human EP4) gene polymorphism with several human immune inflammatory disorders like multiple sclerosis and inflammatory bowel disease. Our findings have provided an insight how inflammatory mediators such as PGE2 are involved in immune response and suggest a novel therapeutic strategy for autoimmune and chronic inflammation by targeting PGE2 receptors.
Chengcan Yao received his PhD in Biomedical Science from Kyoto University at 2010. He then did his post-doc with Professor Shuh Narumiya at Kyoto University as a JSPS (Japan Society for the Promotion of Science) Postdoctoral Fellow for Overseas Researchers. From 2013, Chengcan established his independent research at the MRC Centre for Inflammation Research (CIR) in the University of Edinburgh as a Chancellor's Fellowship.