{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:58Z","timestamp":1791231178875,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Filarial nematodes infect over 200 million people, predominantly stimulating a Type 2 immune response. Protective immunity takes decades to become effective due to dominant immune suppression that develops during infection. Using\n                    <jats:italic>Litomosoides sigmodontis<\/jats:italic>\n                    infection as a murine model of filariasis, we previously demonstrated that PD\u20101 co\u2010inhibition causes Th2 cells to become intrinsically dysfunctional or hypo\u2010responsive during infection, resulting in impaired protective immunity. \u03a4his study demonstrates that Th2 cell\u2010intrinsic hypo\u2010responsiveness is associated with a loss of GATA\u20103 expression by CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from WT, but not PD\u2010L2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. PD\u2010L2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were more resistant to\n                    <jats:italic>L. sigmodontis<\/jats:italic>\n                    and had increased Th2 cell\u2010intrinsic functional quality. CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells expressed PD\u2010L2, and Jh\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    B cell\u2010deficient mice were more resistant to infection. However, Th2 cell\u2010intrinsic hypo\u2010responsiveness still developed in Jh\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, and restricting PD\u2010L2 deficiency to B cells using bone marrow chimaeras did not alter resistance to\n                    <jats:italic>L. sigmodontis<\/jats:italic>\n                    or Th2 cell\u2010intrinsic functional quality. Together, these data indicate that PD\u2010L2 inhibits protective immunity to\n                    <jats:italic>L. sigmodontis<\/jats:italic>\n                    , downregulates GATA\u20103 in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and induces Th2 cell\u2010intrinsic hypo\u2010responsiveness. Whilst B cells play a suppressive role during infection, this is independent of PD\u2010L2 and B cells do not instigate Th2 cell\u2010intrinsic hypo\u2010responsiveness.\n                  <\/jats:p>","DOI":"10.1002\/eji.70021","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T07:06:41Z","timestamp":1754291201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PD\u2010L2 Inhibits Protective Immunity, Th2 Cell Functional Quality, and GATA\u20103 Expression During Filarial Nematode Infection"],"prefix":"10.1002","volume":"55","author":[{"given":"Johanna A.","family":"Knipper","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research University of Edinburgh  Edinburgh UK"},{"name":"Max Planck Institute of Immunobiology and Epigenetics  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon M.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-066X","authenticated-orcid":false,"given":"Judith E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research University of Edinburgh  Edinburgh UK"},{"name":"Lydia Becker Institute of Immunology and Inflammation School of Biological Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-8189","authenticated-orcid":false,"given":"Matthew D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research University of Edinburgh  Edinburgh 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