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ILC2s are also implicated in the development of type 2 inflammation\u2013mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127\u2212CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127\u2212CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.<\/jats:p>","DOI":"10.1084\/jem.20231827","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T02:21:01Z","timestamp":1715912461000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Human CD127 negative ILC2s show immunological memory"],"prefix":"10.1084","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-6851","authenticated-orcid":true,"given":"Laura","family":"Math\u00e4","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056d84691","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology, Tumor and Cell Biology, Karolinska Institute 1 , Stockholm, Sweden"},{"name":"Terry Fox Laboratory, British Columbia Cancer 2 , Vancouver, 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