{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T19:24:00Z","timestamp":1773516240398,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2013dependent 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\u2013deficient (WSX-1\u2212\/\u2212) 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1202916","type":"journal-article","created":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T03:58:14Z","timestamp":1364443094000},"page":"4553-4561","source":"Crossref","is-referenced-by-count":24,"title":["IL-27 Receptor Signaling Regulates CD4+ T Cell Chemotactic Responses during Infection"],"prefix":"10.1093","volume":"190","author":[{"given":"Emily","family":"Gwyer Findlay","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Villegas-Mendez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Brian","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT,","place":["United Kingdom"]},{"name":"Department of Immunology and Molecular Pathology, University College London Medical School , London, W1T 4JF,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colette A","family":"Inkson","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester , Manchester, M13 9PT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tovah N","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiaan J","family":"Saris","sequence":"additional","affiliation":[{"name":"Department of Inflammation Research , Amgen, Thousand Oaks, CA 91320"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor M","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin N","family":"Couper","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,5,1]]},"reference":[{"key":"2025032406572310100_r1","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1189\/jlb.0609445","article-title":"Interleukin 27: a double-edged sword for offense and defense","volume":"86","author":"Yoshida","year":"2009","journal-title":"J. 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