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However, their roles in human innate lymphoid cell (ILC) function remain unclear. Here, we found that Ikaros (\n                    <jats:italic>IKZF1<\/jats:italic>\n                    ) is expressed by all ILC subsets, including NK cells, in blood, tonsil, and gut, while Helios (\n                    <jats:italic>IKZF2<\/jats:italic>\n                    ) is preferentially expressed by ILC3 in tonsil and gut. Aiolos (\n                    <jats:italic>IKZF3<\/jats:italic>\n                    ) followed the expression pattern of T\u2010bet and Eomes, being predominantly expressed by ILC1 and NK cells. Differentiation of IFN\u2010\u03b3\u2010producing ILC1 and NK cells from ILC3 by IL\u20101\u03b2 plus IL\u201012\u2010stimulation was associated with upregulation of T\u2010bet and Aiolos. Selective degradation of Aiolos and Ikaros by lenalidomide suppressed ILC1 and NK cell differentiation and expression of ILC1 and NK cell\u2010related transcripts (\n                    <jats:italic>LEF1<\/jats:italic>\n                    ,\n                    <jats:italic>PRF1<\/jats:italic>\n                    ,\n                    <jats:italic>GRZB<\/jats:italic>\n                    ,\n                    <jats:italic>CD244<\/jats:italic>\n                    ,\n                    <jats:italic>NCR3<\/jats:italic>\n                    , and\n                    <jats:italic>IRF8<\/jats:italic>\n                    ). In line with reduced ILC1\/NK cell differentiation, we observed an increase in the expression of the ILC3\u2010related TF Helios, as well as ILC3 transcripts (\n                    <jats:italic>TNFSF13B<\/jats:italic>\n                    ,\n                    <jats:italic>IL22<\/jats:italic>\n                    ,\n                    <jats:italic>NRP1<\/jats:italic>\n                    , and\n                    <jats:italic>RORC<\/jats:italic>\n                    ) and in the frequency of IL\u201022 producing ILC3 in cultures with IL\u20101\u03b2 and IL\u201023. These data suggest that suppression of Aiolos and Ikaros expression inhibits ILC1 and NK cell differentiation while ILC3 function is maintained. Hence, our results open up for new possibilities in targeting Ikaros family TFs for modulation of type 1\/3 immunity in inflammation and cancer.\n                  <\/jats:p>","DOI":"10.1002\/eji.201848075","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T02:08:48Z","timestamp":1559268528000},"page":"1344-1355","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Suppression of Aiolos and Ikaros expression by lenalidomide reduces human ILC3\u2212ILC1\/NK cell transdifferentiation"],"prefix":"10.1002","volume":"49","author":[{"given":"Luca","family":"Mazzurana","sequence":"first","affiliation":[{"name":"Center for Infectious Medicine Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Forkel","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine Department of 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