WSX-1 Signalling Inhibits CD4+ T Cell Migration to the Liver during Malaria Infection by Repressing Chemokine-Independent Pathways: e78486

• Published in: PloS one 2013-11, Vol.8 (11)
• Main Authors: Villegas-Mendez, Ana, Findlay, Emily Gwyer, Souza, J Briande, Grady, Lisa-Marie, Saris, Christiaan J, Lane, Thomas E, Riley, Eleanor M, Couper, Kevin N
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0078486

IL-27 is an important and non-redundant regulator of effector T cell accumulation in non-lymphoid tissues during infection. Using malaria as a model systemic pro-inflammatory infection, we demonstrate that the aberrant accumulation of CD4+ T cells in the liver of infected IL27R-/- (WSX-1-/-) mice is a result of differences in cellular recruitment, rather than changes in T cell proliferation or cell death. We show that IL-27 both inhibits the migratory capacity of infection-derived CD4+ T cells towards infection-derived liver cells, but also suppresses the production of soluble liver-derived mediator(s) that direct CD4+ T cell movement towards the inflamed tissue. Although CCL4 and CCL5 expression was higher in livers of infected WSX-1-/- mice than infected WT mice, and hepatic CD4+ T cells from WSX-1-/- mice expressed higher levels of CCR5 than cells from WT mice, migration of CD4+ T cells to the liver of WSX-1-/- mice during infection was not controlled by chemokine (R) signalling. However, anti-IL-12p40 treatment reduced migration of CD4+ T cells towards infection-derived liver cells, primarily by abrogating the hepatotropic migratory capacity of T cells, rather than diminishing soluble tissue-derived migratory signals. These results indicate that IL-27R signalling restricts CD4+ T cell accumulation within the liver during infection primarily by suppressing T cell chemotaxis, which may be linked to its capacity to repress Th1 differentiation, as well as by inhibiting the production of soluble, tissue-derived chemotaxins.