| First Author | Villegas-Mendez A | Year | 2013 |
| Journal | PLoS Pathog | Volume | 9 |
| Issue | 4 | Pages | e1003293 |
| PubMed ID | 23593003 | Mgi Jnum | J:196654 |
| Mgi Id | MGI:5488993 | Doi | 10.1371/journal.ppat.1003293 |
| Citation | Villegas-Mendez A, et al. (2013) IL-27 receptor signalling restricts the formation of pathogenic, terminally differentiated Th1 cells during malaria infection by repressing IL-12 dependent signals. PLoS Pathog 9(4):e1003293 |
| abstractText | The IL-27R, WSX-1, is required to limit IFN-gamma production by effector CD4(+) T cells in a number of different inflammatory conditions but the molecular basis of WSX-1-mediated regulation of Th1 responses in vivo during infection has not been investigated in detail. In this study we demonstrate that WSX-1 signalling suppresses the development of pathogenic, terminally differentiated (KLRG-1(+)) Th1 cells during malaria infection and establishes a restrictive threshold to constrain the emergent Th1 response. Importantly, we show that WSX-1 regulates cell-intrinsic responsiveness to IL-12 and IL-2, but the fate of the effector CD4(+) T cell pool during malaria infection is controlled primarily through IL-12 dependent signals. Finally, we show that WSX-1 regulates Th1 cell terminal differentiation during malaria infection through IL-10 and Foxp3 independent mechanisms; the kinetics and magnitude of the Th1 response, and the degree of Th1 cell terminal differentiation, were comparable in WT, IL-10R1(-)/(-) and IL-10(-)/(-) mice and the numbers and phenotype of Foxp3(+) cells were largely unaltered in WSX-1(-)/(-) mice during infection. As expected, depletion of Foxp3(+) cells did not enhance Th1 cell polarisation or terminal differentiation during malaria infection. Our results significantly expand our understanding of how IL-27 regulates Th1 responses in vivo during inflammatory conditions and establishes WSX-1 as a critical and non-redundant regulator of the emergent Th1 effector response during malaria infection. |
