{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:59:28Z","timestamp":1772780368448,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T00:00:00Z","timestamp":1426464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"JSPS KAKENHI","award":["21591241"],"award-info":[{"award-number":["21591241"]}]},{"name":"JSPS KAKENHI","award":["25461450"],"award-info":[{"award-number":["25461450"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>Mammals have evolved to protect their offspring during early fetal development. Elaborated mechanisms induce tolerance in the maternal immune system for the fetus. Female hormones, mainly estrogen, play a role in suppressing maternal lymphopoiesis. However, the molecular mechanisms involved in the maternal immune tolerance are largely unknown. Here, we show that estrogen\u2010induced soluble Frizzled\u2010related proteins (sFRPs), and particularly sFRP5, suppress B\u2010lymphopoiesis in vivo in transgenic mice. Mice overexpressing sFRP5 had fewer B\u2010lymphocytes in the peripheral blood and spleen. High levels of sFRP5 inhibited early B\u2010cell differentiation in the bone marrow (BM), resulting in the accumulation of cells with a common lymphoid progenitor (CLP) phenotype. Conversely, sFRP5 deficiency reduced the number of hematopoietic stem cells (HSCs) and primitive lymphoid progenitors in the BM, particularly when estrogen was administered. Furthermore, a significant reduction in CLPs and B\u2010lineage\u2010committed progenitors was observed in the BM of <jats:italic>sfrp5<\/jats:italic>\u2010null pregnant females. We concluded that, although high sFRP5 expression inhibits B\u2010lymphopoiesis in vivo, physiologically, it contributes to the preservation of very primitive lymphopoietic progenitors, including HSCs, under high estrogen levels. Thus, sFRP5 regulates early lympho\u2010hematopoiesis in the maternal BM, but the maternal\u2013fetal immune tolerance still involves other molecular mechanisms that remain to be uncovered.<\/jats:p>","DOI":"10.1002\/eji.201444939","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T12:52:55Z","timestamp":1423831975000},"page":"1390-1401","source":"Crossref","is-referenced-by-count":7,"title":["Estrogen\u2010inducible sFRP5 inhibits early B\u2010lymphopoiesis in vivo, but not during pregnancy"],"prefix":"10.1002","volume":"45","author":[{"given":"Takafumi","family":"Yokota","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Oritani","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Sudo","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Doi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Habuchi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Ichii","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Okuzaki","sequence":"additional","affiliation":[{"name":"DNA\u2010chip Development Center for Infectious Diseases Research Institute for Microbial Diseases Osaka University  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuma","family":"Tomizuka","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin California Inc. Research Divisions  CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Yamawaki","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin Co Ltd. Biologics Research Laboratories Research Division  Machida Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Kakitani","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin Co Ltd. Bio Process Research and Development Laboratories  Takasaki Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Shimono","sequence":"additional","affiliation":[{"name":"TransGenic Inc. 7\u20101\u201014 Minatojima\u2010minami  Chuo Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Morii","sequence":"additional","affiliation":[{"name":"Department of Pathology Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Kincade","sequence":"additional","affiliation":[{"name":"Immunobiology and Cancer Program Oklahoma Medical Research Foundation  Oklahoma City OK USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzuru","family":"Kanakura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.5.1507"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1996.tb00052.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5382"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.7.3409"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2000.imr017502.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044532302000738"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6061"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00623"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.065839"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.05.020"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35083601"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.018"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2360"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.018"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni083"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20369"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.03.014"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.07.010"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.013"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80453-5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.09.067"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.01.003"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.12.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.07.017"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81921-2"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81922-4"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11196"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1547"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1811"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004708107"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2794"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.09.016"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.16180"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00451"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12932"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","first-page":"6355","DOI":"10.4049\/jimmunol.163.12.6355","article-title":"Absence of expression of RAG1 in peritoneal B\u20101 cells detected by knocking into RAG1 locus with green fluorescent protein gene","volume":"163","author":"Kuwata N.","year":"1999","journal-title":"J. Immunol."},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.6.2059"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.013"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00366-7"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201444939","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201444939","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201444939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T18:23:26Z","timestamp":1696616606000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201444939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,16]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1002\/eji.201444939"],"URL":"https:\/\/doi.org\/10.1002\/eji.201444939","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,16]]}}}