{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:25:00Z","timestamp":1790166300088,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Summary<\/jats:title>\n \n Background<\/jats:title>\n \n Retinoic acid (\n RA<\/jats:styled-content>\n ), the main biologically active metabolite of vitamin A, is known to promote gut homing of lymphocytes, as well as various regulatory and effector immune responses. In contrast, the active form of vitamin D, 1,25\u2010dihydroxyvitamin D\n 3<\/jats:sub>\n (1,25D3), is predominantly immunosuppressive. Little is known about the direct effects of these vitamins on the recently identified innate lymphoid cells (\n ILC<\/jats:styled-content>\n s).\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n We sought to characterize the effects of\n RA<\/jats:styled-content>\n and 1,25D3 on human\n ILC<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Peripheral blood mononuclear cells were isolated from 27 non\u2010selected blood donor buffy coats, and\n ILC<\/jats:styled-content>\n s were sorted by\n FACS<\/jats:styled-content>\n .\n ILC<\/jats:styled-content>\n 1,\n ILC<\/jats:styled-content>\n 2, and\n ILC<\/jats:styled-content>\n 3 cells were cultured for 5\u00a0days with\n RA<\/jats:styled-content>\n , 1,25D3, and various cytokines known to activate\n ILC<\/jats:styled-content>\n s (\n IL<\/jats:styled-content>\n \u20102,\n IL<\/jats:styled-content>\n \u20107,\n IL<\/jats:styled-content>\n \u201012, thymic stromal lymphopoietin (\n TSLP<\/jats:styled-content>\n ),\n IL<\/jats:styled-content>\n \u201025, and\n IL<\/jats:styled-content>\n \u201033). Cytokines produced by\n ILC<\/jats:styled-content>\n s were measured in culture supernatants, and surface receptor expression was analysed by flow cytometry.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Retinoic acid acted synergistically with\n IL<\/jats:styled-content>\n \u20102 and other activating cytokines to induce expression of the gut\u2010homing integrin \u03b14\u03b27 in\n ILC<\/jats:styled-content>\n s, as well as production of\n IL<\/jats:styled-content>\n \u20105 and\n IL<\/jats:styled-content>\n \u201013 in\n ILC<\/jats:styled-content>\n 2 cells, and\n IFN<\/jats:styled-content>\n \u2010\u03b3 in\n ILC<\/jats:styled-content>\n 1 and\n ILC<\/jats:styled-content>\n 3 cells. Expression of integrin \u03b14\u03b27 and cytokine production in\n ILC<\/jats:styled-content>\n s stimulated with\n RA<\/jats:styled-content>\n \u00a0+\u00a0\n IL<\/jats:styled-content>\n \u20102 was increased at least fourfold as compared to\n ILC<\/jats:styled-content>\n s cultured with\n RA<\/jats:styled-content>\n or\n IL<\/jats:styled-content>\n \u20102 alone. In contrast,\n RA<\/jats:styled-content>\n completely inhibited the\n IL<\/jats:styled-content>\n \u20102\u2010induced expression of cutaneous lymphocyte antigen (\n CLA<\/jats:styled-content>\n ) in\n ILC<\/jats:styled-content>\n s. Moreover, addition of 1,25D3 to\n ILC<\/jats:styled-content>\n s cultured with\n RA<\/jats:styled-content>\n \u00a0+\u00a0\n IL<\/jats:styled-content>\n \u20102 inhibited cytokine production and expression of integrin \u03b14\u03b27 by at least 30%.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Retinoic acid and 1,25D3 have antagonistic effects on the expression of effector cytokines and gut\u2010homing integrin by human\n ILC<\/jats:styled-content>\n s. The balance between these vitamins may be an important factor in the functioning of\n ILC<\/jats:styled-content>\n s and the diseases in which\n ILC<\/jats:styled-content>\n s are implicated, such as allergic inflammation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cea.12568","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T21:44:49Z","timestamp":1431121489000},"page":"1214-1225","source":"Crossref","is-referenced-by-count":68,"title":["Vitamins A and D have antagonistic effects on expression of effector cytokines and gut\u2010homing integrin in human innate lymphoid cells"],"prefix":"10.1111","volume":"45","author":[{"given":"B.","family":"Ruiter","sequence":"first","affiliation":[{"name":"Center for Immunology & Inflammatory Diseases Massachusetts General Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. U.","family":"Patil","sequence":"additional","affiliation":[{"name":"Center for Immunology & Inflammatory Diseases Massachusetts General Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"},{"name":"Food Allergy Center Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. G.","family":"Shreffler","sequence":"additional","affiliation":[{"name":"Center for Immunology & Inflammatory Diseases Massachusetts General Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"},{"name":"Food Allergy Center Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075053"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3365"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2534"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2104"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.015"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005374"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.146"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-427781"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.3.446-464.2005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303245"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.011"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-135251"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132742"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070590"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.3724"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.003"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-7961-11-4"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-7-27"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002883"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121588"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13158"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2378"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-013-8361-3"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.12.1562"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.10.3385"},{"key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"1704S","DOI":"10.1093\/jn\/125.suppl_6.1704S","article-title":"Immunosuppressive 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