| First Author | Montes de Oca M | Year | 2020 |
| Journal | PLoS Pathog | Volume | 16 |
| Issue | 10 | Pages | e1008994 |
| PubMed ID | 33049000 | Mgi Jnum | J:337623 |
| Mgi Id | MGI:6728240 | Doi | 10.1371/journal.ppat.1008994 |
| Citation | Montes de Oca M, et al. (2020) IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection. PLoS Pathog 16(10):e1008994 |
| abstractText | Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNgamma-producing Tbet+ CD4+ T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4+ T cells, but the underlying mechanisms of these immunoregulatory pathways are not clear. Here we studied the role of IL-27 signalling in experimental visceral leishmaniasis (VL) caused by infection of C57BL/6 mice with the human pathogen Leishmania donovani. We found IL-27 signalling was critical for the development of IL-10-producing Th1 (Tr1) cells during infection. Furthermore, in the absence of IL-27 signalling, there was improved control of parasite growth, but accelerated splenic pathology characterised by the loss of marginal zone macrophages. Critically, we discovered that IL-27 signalling limited glycolysis in Th1 cells during infection that in turn attenuated inflammation. Furthermore, the modulation of glycolysis in the absence of IL-27 signalling restricted tissue pathology without compromising anti-parasitic immunity. Together, these findings identify a novel mechanism by which IL-27 mediates immune regulation during disease by regulating cellular metabolism. |
