{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:57:26Z","timestamp":1791824246217,"version":"4.3.4"},"posted":{"date-parts":[[2026,5,26]]},"group-title":"Evolutionary Biology","reference-count":152,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/032atxq54","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2R35GM128822"],"award-info":[{"award-number":["2R35GM128822"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32GM142607"],"award-info":[{"award-number":["T32GM142607"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Species differ markedly in how they regulate immune responses, yet the molecular basis of this variation remains incompletely understood. Here, we characterize an underexplored regulatory mechanism of the pro-inflammatory IL-18 pathway, centered on a truncated\n                  <jats:italic>IL18R1<\/jats:italic>\n                  isoform with striking species-specific expression differences. This isoform,\n                  <jats:italic>IL18R1-Short<\/jats:italic>\n                  , derives from an ancient LINE2 retrotransposon insertion that provides an intronic polyadenylation signal, producing a receptor that lacks the intracellular signaling domain. Using RNA sequencing across nine mammals, we find that although this cis-regulatory element is broadly conserved, robust\n                  <jats:italic>IL18R1-Short<\/jats:italic>\n                  expression is species- and tissue-restricted: bats and mice express it at high levels, particularly in barrier tissues (lung, skin, intestine), whereas most other species, including humans, show little or no expression. Functionally, IL18R1-Short dampens IL-18\u2013induced NF\u03baB signaling in human, mouse, and bat systems, and knockdown of the mouse ortholog enhances IL-18\u2013driven immune and inflammatory gene expression in mouse T cells. Together, these results identify IL18R1-Short as a transposable element-derived decoy receptor and highlight alternative transcription as a source of species-specific immune regulation.\n                <\/jats:p>","DOI":"10.64898\/2026.05.25.727421","type":"posted-content","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T05:45:15Z","timestamp":1779860715000},"source":"Crossref","is-referenced-by-count":1,"title":["An ancient retrotransposon provides species-specific tuning of IL-18 inflammatory signaling"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-5673","authenticated-orcid":false,"given":"Andrea D.","family":"Ordonez","sequence":"first","affiliation":[{"name":"BioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO. 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7014-1349","authenticated-orcid":false,"given":"Holly","family":"Allen","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO. 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-556X","authenticated-orcid":false,"given":"Lynn","family":"Sanford","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO. 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-9876","authenticated-orcid":false,"given":"Atma","family":"Ivancevic","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute and Department of Molecular, Cellular 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