{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T02:10:24Z","timestamp":1794103824700,"version":"4.8.0"},"reference-count":71,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"70","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:p>\n            Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of na\u00efve-like ILCs suggests an ILC differentiation process that is akin to na\u00efve T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here, we showed that tonsillar ILCs expressing CD45RA lacked proliferative activity, indicative of cellular quiescence. CD62L distinguished two subsets of CD45RA\n            <jats:sup>+<\/jats:sup>\n            ILCs. CD45RA\n            <jats:sup>+<\/jats:sup>\n            CD62L\n            <jats:sup>+<\/jats:sup>\n            ILCs (CD62L\n            <jats:sup>+<\/jats:sup>\n            ILCs) resembled circulating na\u00efve ILCs because they lacked the transcriptional, metabolic, epigenetic, and cytokine production signatures of differentiated ILCs. CD45RA\n            <jats:sup>+<\/jats:sup>\n            CD62L\n            <jats:sup>\u2212<\/jats:sup>\n            ILCs (CD62L\n            <jats:sup>\u2212<\/jats:sup>\n            ILCs) were epigenetically similar to CD62L\n            <jats:sup>+<\/jats:sup>\n            ILCs but showed a transcriptional, metabolic, and cytokine production signature that was more akin to differentiated ILCs. CD62L\n            <jats:sup>+<\/jats:sup>\n            and CD62L\n            <jats:sup>\u2212<\/jats:sup>\n            ILCs contained uni- and multipotent precursors of ILC1s\/NK cells and ILC3s. Differentiation of CD62L\n            <jats:sup>+<\/jats:sup>\n            and CD62L\n            <jats:sup>\u2212<\/jats:sup>\n            ILCs led to metabolic reprogramming including up-regulation of genes associated with glycolysis, which was needed for their effector functions after differentiation. CD62L\n            <jats:sup>\u2212<\/jats:sup>\n            ILCs with preferential differentiation capacity toward IL-22\u2013producing ILC3s accumulated in the inflamed mucosa of patients with inflammatory bowel disease. These data suggested distinct differentiation potential of CD62L\n            <jats:sup>+<\/jats:sup>\n            and CD62L\n            <jats:sup>\u2212<\/jats:sup>\n            ILCs between tissue microenvironments and identified that manipulation of these cells is a possible approach to restore tissue-immune homeostasis.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abj8301","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T17:57:15Z","timestamp":1650045435000},"source":"Crossref","is-referenced-by-count":40,"title":["CD45RA\n            <sup>+<\/sup>\n            CD62L\n            <sup>\u2212<\/sup>\n            ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs"],"prefix":"10.1126","volume":"7","author":[{"given":"Efthymia","family":"Kokkinou","sequence":"first","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-4346","authenticated-orcid":true,"given":"Ram Vinay","family":"Pandey","sequence":"additional","affiliation":[{"name":"Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6951-303X","authenticated-orcid":true,"given":"Luca","family":"Mazzurana","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9952-3383","authenticated-orcid":true,"given":"Irene","family":"Gutierrez-Perez","sequence":"additional","affiliation":[{"name":"Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-7700","authenticated-orcid":true,"given":"Christopher Andrew","family":"Tibbitt","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Weigel","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5207-6715","authenticated-orcid":true,"given":"Tea","family":"Soini","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-1583","authenticated-orcid":true,"given":"Anna","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rao","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-6450","authenticated-orcid":true,"given":"Suzanne M.","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-2026","authenticated-orcid":true,"given":"Mattias","family":"Jangard","sequence":"additional","affiliation":[{"name":"ENT Unit, Sophiahemmet University Research Laboratory and Sophiahemmet Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-1292","authenticated-orcid":true,"given":"Danielle","family":"Friberg","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Uppsala University, Uppsala, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4239-8419","authenticated-orcid":true,"given":"Ulrik","family":"Lindforss","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Pelvic Cancer, GI Oncology and Colorectal Surgery Unit, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Nordenvall","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Pelvic Cancer, GI Oncology and Colorectal Surgery Unit, 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