{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:50:55Z","timestamp":1775976655508,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,25]]},"group-title":"Immunology","reference-count":76,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI146188"],"award-info":[{"award-number":["AI146188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI133041"],"award-info":[{"award-number":["AI133041"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["GM13096"],"award-info":[{"award-number":["GM13096"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Intestinal intraepithelial lymphocytes (IELs) are a versatile population of immune cells with both effector and regulatory roles in gut immunity. Although this functional diversity is thought to arise from distinct IEL subpopulations, the heterogeneity of TCR\u03b1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  and TCR\u03b3\u03b4\n                  <jats:sup>+<\/jats:sup>\n                  IELs have not been well-characterized. Using scRNAseq, we identified CD8\u03b1\u03b1\n                  <jats:sup>+<\/jats:sup>\n                  T cell subsets with memory-like (\n                  <jats:italic>Tcf7<\/jats:italic>\n                  \u207a) and effector-like (\n                  <jats:italic>Prdm1<\/jats:italic>\n                  \u207a) profiles in both TCR\u03b1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  and TCR\u03b3\u03b4\n                  <jats:sup>+<\/jats:sup>\n                  IELs. Using CD160 and CD122 as markers of memory-like and effector-like cells, respectively, we found that while effector-like cells dominated the small intestine, memory-like IELs were more prevalent in the large intestine, suggesting a functional specialization of immune responses along the gut. Further transcriptional analysis revealed shared profiles between TCR\u03b1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  and TCR\u03b3\u03b4\n                  <jats:sup>+<\/jats:sup>\n                  small intestinal IEL subsets, suggesting conserved functional roles across these populations. Finally, our analysis indicated that TCR\u03b1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  memory-like IELs arise from\n                  <jats:italic>Tcf7\u207a<\/jats:italic>\n                  double-negative (DN) precursors, and that effector-like IELs subsequently differentiate from the memory-like population. In contrast, TCR\u03b3\u03b4\n                  <jats:sup>+<\/jats:sup>\n                  IELs appear to originate from two distinct precursor populations, one expressing\n                  <jats:italic>Tcf7<\/jats:italic>\n                  and the other\n                  <jats:italic>Zeb2<\/jats:italic>\n                  , indicating the presence of parallel developmental pathways within this lineage. Overall, our findings reveal that both TCR\u03b1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  and TCR\u03b3\u03b4\n                  <jats:sup>+<\/jats:sup>\n                  cells contain memory-like and effector-like subsets, which may contribute to the functional heterogeneity of IELs.\n                <\/jats:p>","DOI":"10.1101\/2025.05.20.655135","type":"posted-content","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T15:50:16Z","timestamp":1748188216000},"source":"Crossref","is-referenced-by-count":0,"title":["Heterogeneity of CD8\u03b1\u03b1 intraepithelial lymphocytes is transcriptionally conserved between TCR\u03b1\u03b2 and TCR\u03b3\u03b4 cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-8899","authenticated-orcid":false,"given":"Kaito A.","family":"Hioki","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology Program, University of Massachusetts, Amherst MA, USA"},{"name":"Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, USA"},{"name":"UMass Biotech Training Program (BTP), Amherst, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8983-2118","authenticated-orcid":false,"given":"Xueting","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, USA"},{"name":"Animal Biotechnology and Biomedical Sciences Program, University of Massachusetts, Amherst, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4518-4392","authenticated-orcid":false,"given":"Adam C.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, USA"},{"name":"UMass Biotech Training Program (BTP), Amherst, MA, USA"},{"name":"Animal Biotechnology and Biomedical Sciences Program, University of Massachusetts, Amherst, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Ranjan","sequence":"additional","affiliation":[{"name":"Genomics Resource Laboratory, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-8732","authenticated-orcid":false,"given":"Elena L.","family":"Pobezinskaya","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6115-3559","authenticated-orcid":false,"given":"Leonid A.","family":"Pobezinsky","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Program, University of Massachusetts, Amherst MA, USA"},{"name":"Department of Veterinary and Animal Science, University 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