IL-27 Receptor Signaling Regulates CD4+ T Cell Chemotactic Responses during Infection.


Gwyer Findlay, E; Villegas-Mendez, A; de Souza, JB; Inkson, CA; Shaw, TN; Saris, CJ; Hunter, CA; Riley, EM; Couper, KN; (2013) IL-27 Receptor Signaling Regulates CD4+ T Cell Chemotactic Responses during Infection. Journal of immunology (Baltimore, Md, 190 (9). pp. 4553-61. ISSN 0022-1767 DOI: https://doi.org/10.4049/jimmunol.1202916

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Abstract

: IL-27 exerts pleiotropic suppressive effects on naive and effector T cell populations during infection and inflammation. Surprisingly, however, the role of IL-27 in restricting or shaping effector CD4(+) T cell chemotactic responses, as a mechanism to reduce T cell-dependent tissue inflammation, is unknown. In this study, using Plasmodium berghei NK65 as a model of a systemic, proinflammatory infection, we demonstrate that IL-27R signaling represses chemotaxis of infection-derived splenic CD4(+) T cells in response to the CCR5 ligands, CCL4 and CCL5. Consistent with these observations, CCR5 was expressed on significantly higher frequencies of splenic CD4(+) T cells from malaria-infected, IL-27R-deficient (WSX-1(-/-)) mice than from infected wild-type mice. We find that IL-27 signaling suppresses splenic CD4(+) T cell CCR5-dependent chemotactic responses during infection by restricting CCR5 expression on CD4(+) T cell subtypes, including Th1 cells, and also by controlling the overall composition of the CD4(+) T cell compartment. Diminution of the Th1 response in infected WSX-1(-/-) mice in vivo by neutralization of IL-12p40 attenuated CCR5 expression by infection-derived CD4(+) T cells and also reduced splenic CD4(+) T cell chemotaxis toward CCL4 and CCL5. These data reveal a previously unappreciated role for IL-27 in modulating CD4(+) T cell chemotactic pathways during infection, which is related to its capacity to repress Th1 effector cell development. Thus, IL-27 appears to be a key cytokine that limits the CCR5-CCL4/CCL5 axis during inflammatory settings.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 23536628
Web of Science ID: 317907900020
URI: http://researchonline.lshtm.ac.uk/id/eprint/748747

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