{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:32:44Z","timestamp":1791099164988,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,2,8]]},"abstract":"<jats:p>\n                    Steady-state development of plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) requires the ligand for FMS-like tyrosine kinase 3 receptor (flt3L), but little is known about how other cytokines may also control this process. In this study, we show that IL-2 inhibits the development of both pDCs and cDCs from bone marrow cells under flt3L stimulation, by acting on lineage\n                    <jats:sup>\u2212<\/jats:sup>\n                    flt3\n                    <jats:sup>+<\/jats:sup>\n                    precursors. This inhibition of DC development by IL-2 requires IL-2R\u03b1 and IL2R\u03b2. IL-2R\u03b1 is specifically expressed in one stage of the DC precursor: the monocyte and DC progenitors (MDPs). Furthermore, more MDPs are found in flt3L-stimulated bone marrow cultures when IL-2 is present, suggesting that IL-2 may be inhibiting DC development at the MDP stage. Consistent with our in vitro findings, we observe that nonobese diabetic (NOD) mice, which express less IL-2 compared with diabetes-resistant NOD.\n                    <jats:italic>Idd3\/5<\/jats:italic>\n                    mice, have more splenic pDCs. Additionally, DCs developed in vitro in the presence of flt3L and IL-2 display reduced ability to stimulate T-cell proliferation compared with DCs developed in the presence of flt3L alone. Although the addition of IL-2 does not increase the apoptosis of DCs during their development, DCs developed in the presence of IL-2 are more prone to apoptosis upon interaction with T cells. Together our data show that IL-2 can inhibit both the development and the function of DCs. This pathway may have implications for the loss of immune tolerance: Reduced IL-2 signaling may lead to increased DC number and T-cell stimulatory capacity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1009738108","type":"journal-article","created":{"date-parts":[[2011,1,25]],"date-time":"2011-01-25T01:09:22Z","timestamp":1295917762000},"page":"2408-2413","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["Interleukin-2 inhibits FMS-like tyrosine kinase 3 receptor ligand (flt3L)-dependent development and function of conventional and plasmacytoid dendritic cells"],"prefix":"10.1073","volume":"108","author":[{"given":"Annie W.","family":"Lau-Kilby","sequence":"first","affiliation":[{"name":"Immune Tolerance Section, Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosima C.","family":"Kretz","sequence":"additional","affiliation":[{"name":"Immune Tolerance Section, Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Pechhold","sequence":"additional","affiliation":[{"name":"Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Price","sequence":"additional","affiliation":[{"name":"Immune Tolerance Section, Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Dorta","sequence":"additional","affiliation":[{"name":"Immune Tolerance Section, Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haydee","family":"Ramos","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Trinchieri","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin V.","family":"Tarbell","sequence":"additional","affiliation":[{"name":"Immune Tolerance Section, Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,1,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231606698"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090746"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1122545"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030323"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.11.3489"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1141"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.10.009"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1170540"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270107"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1340"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.02.013"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020045"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.04.004"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1958"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.03.016"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901524"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.5.3260"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3746"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2004.06.010"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/369333a0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.6592"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-127480"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900428"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271234"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/353858a0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00879.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2008.84"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.10.6457"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092627"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101664"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115843"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806439105"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8100367"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012646"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.01.008"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn036"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.2001.0400"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323676"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1662"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.11.4106-4114.2000"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1009738108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:20:32Z","timestamp":1649794832000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1009738108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,24]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,2,8]]}},"alternative-id":["10.1073\/pnas.1009738108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1009738108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,24]]},"assertion":[{"value":"2011-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}