{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:44:01Z","timestamp":1792043041887,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study presents the discovery and first functional characterization of chicken lipid\u2010reactive Natural Killer T (NKT)\u2010like cells, resolving a long\u2010standing knowledge gap in avian immunology. Using purified TCRV\u03b22\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes, we demonstrate through rigorous experiments combining shRNA\u2010mediated gene silencing, pharmacological pathway blockade, primary MACS\u2010purified co\u2010cultures, and intracellular cytokine flow cytometry that these cells are activated by CpG\u2010ODN\u2010stimulated antigen\u2010presenting cells (APCs). Activation selectively depends on APC\u2010driven glycosphingolipid (GSL) biosynthesis, with CpG\u2010ODN significantly upregulating key biosynthetic enzymes (\n                    <jats:italic>ST3GAL1<\/jats:italic>\n                    and\n                    <jats:italic>ST3GAL5<\/jats:italic>\n                    ) in APCs. Silencing of enzymes involved in this pathway or chemical inhibition of GSL synthesis abrogated T cell activation. We identify GM3 as a potent, functional lipid ligand activating TCRV\u03b22\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes. In parallel, IL\u201012 and IL\u201018 trigger IFN\u2010\u03b3 production from TCRV\u03b22\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes, crucially requiring live APC interactions. Upon activation of splenocytes with GM3, the cells expressed\n                    <jats:italic>chIL\u20102<\/jats:italic>\n                    ,\n                    <jats:italic>chIL\u20104<\/jats:italic>\n                    ,\n                    <jats:italic>chIL\u201017<\/jats:italic>\n                    ,\n                    <jats:italic>Granzyme A<\/jats:italic>\n                    , and\n                    <jats:italic>Perforin<\/jats:italic>\n                    . By establishing functional, nonpeptide lipid\u2010reactive T cells in chickens, these findings redefine the conceptual framework of avian innate\u2010like T cell immunology. This discovery unlocks a highly translatable, universal target for lipid\u2010adjuvanted poultry vaccines to enhance global animal health and food security.\n                  <\/jats:p>","DOI":"10.1002\/eji.70302","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:44:41Z","timestamp":1792039481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Avian TCRV\u03b22\n                    <sup>+<\/sup>\n                    T Cells Recognizing the Endogenous Ganglioside via a chCD1.1\u2010Dependent Pathway"],"prefix":"10.1002","volume":"56","author":[{"given":"Nitin","family":"Kamble","sequence":"first","affiliation":[{"name":"The Pirbright Institute Pirbright  Woking UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal R","family":"Anjum","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School University of Bristol  Langford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahriar","family":"Behboudi","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Pirbright  Woking UK"},{"name":"Bristol Veterinary School University of Bristol  Langford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ni.3298","article-title":"The Burgeoning Family of Unconventional T Cells","volume":"16","author":"Godfrey D. I.","year":"2015","journal-title":"Nature Immunology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.3389\/fimmu.2018.01393","article-title":"Invariant Natural Killer T Cell Subsets\u2014More than Just Developmental Intermediates","volume":"9","author":"Krovi S. H.","year":"2018","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_11_4_1","first-page":"236","article-title":"Natural Killer T Cells in Health and Disease","volume":"3","author":"Wu L.","year":"2011","journal-title":"Frontiers in Bioscience (Scholar Edition)"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.3390\/ijms24032743","article-title":"Natural Killer T\u2010Like Cells: Immunobiology and Role in Disease","volume":"24","author":"Almeida J. 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H.","year":"1994","journal-title":"Poultry Science"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1073\/pnas.91.3.1094","article-title":"Identification of T\u2010Cell Receptor Alpha\u2010Chain Genes in the Chicken","volume":"91","author":"G\u00f6bel T. W.","year":"1994","journal-title":"PNAS"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"10956","DOI":"10.1073\/pnas.88.23.10956","article-title":"Two Distinct Alpha Beta T\u2010Cell Lineages Can be Distinguished by the Differential Usage of T\u2010Cell Receptor V Beta Gene Segments","volume":"88","author":"Lahti J. M.","year":"1991","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.4049\/jimmunol.181.7.4452","article-title":"Cutting Edge: The Mechanism of Invariant NKT Cell Responses to Viral Danger Signals","volume":"181","author":"Tyznik A. 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