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Although ILCs are mainly known as tissue-resident cells, their precise localization and interactions with the microenvironment are still unclear. Here we combine a multiplexed immunofluorescence technique and a customized computational, open-source analysis pipeline to unambiguously identify CD127<jats:sup>+<\/jats:sup> ILCs in situ and characterize these cells and their microenvironments. Moreover, we reveal the transcription factor IRF4 as a marker for tonsillar ILC3, and identify conserved stromal landmarks characteristic for ILC localization. We also show that CD127<jats:sup>+<\/jats:sup> ILCs share tissue niches with plasma cells in the tonsil. Our works thus provide a platform for multiparametric histological analysis of ILCs to improve our understanding of ILC biology.<\/jats:p>","DOI":"10.1038\/s41467-021-21994-8","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T13:05:27Z","timestamp":1616159127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Multiplexed histology analyses for the phenotypic and spatial characterization of human innate lymphoid cells"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-3699","authenticated-orcid":false,"given":"Anna","family":"Pascual-Reguant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"K\u00f6hler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronja","family":"Mothes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-3361","authenticated-orcid":false,"given":"Sandy","family":"Bauherr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5960-160X","authenticated-orcid":false,"given":"Daniela C.","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Uecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolin","family":"Holzwarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Kotsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-4980","authenticated-orcid":false,"given":"Maximilian","family":"Seidl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5112-495X","authenticated-orcid":false,"given":"Lars","family":"Philipsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-7463","authenticated-orcid":false,"given":"Chiara","family":"Romagnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8969-5432","authenticated-orcid":false,"given":"Raluca","family":"Niesner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7725-9526","authenticated-orcid":false,"given":"Anja E.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"21994_CR1","doi-asserted-by":"publisher","unstructured":"Spits, H. & Di Santo, J. 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KG, Bergisch Gladbach, Germany. Lars Philipsen is shareholder of M04 Patent\u2014und Beteiligungsgesellschaft Ltd., Magdeburg, Germany. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1737"}}