{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:48:25Z","timestamp":1789865305514,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T00:00:00Z","timestamp":1421625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["1K08DK090281"],"award-info":[{"award-number":["1K08DK090281"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>\n                    Potentially life\u2010threatening enterocolitis is the most frequent complication in children with colonic aganglionosis (Hirschsprung disease, HSCR), and little is known about the mechanisms leading to enterocolitis. Splenic lymphopenia has been reported in the Endothelin Receptor B (Ednrb)\u2010null mouse model of HSCR that develops enterocolitis. In this study, we sought to identify molecular mechanisms underlying this immune phenotype. We employed the\n                    <jats:italic>Ednrb<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse, and the knockout of its ligand, Edn3 (\n                    <jats:italic>\n                      Edn3\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ). The major finding is that enterocolitis in the\n                    <jats:italic>Ednrb<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Edn3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice lead to thymic involution, splenic lymphopenia, and suppression of B lymphopoiesis as a consequence of colonic aganglionosis, not an intrinsic Edn3\u2010Ednrb signaling defect directly affecting the lymphoid organs. We showed that adoptive transfer of\n                    <jats:italic>Ednrb<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    marrow repopulated the RAG2\u2010null mice marrow, thymus and spleen without development of enterocolitis. We identified the glucocorticoid corticosterone, as a potential mediator of the immune phenotype. This previously unrecognized pattern of immune abnormalities in mouse is nearly identical to lymphoid depletion in neonatal sepsis during severe physiological stress, suggesting that the mouse model used here could be also used for sepsis studies.\n                  <\/jats:p>","DOI":"10.1002\/eji.201444737","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T02:25:12Z","timestamp":1418091912000},"page":"807-817","source":"Crossref","is-referenced-by-count":34,"title":["Enterocolitis causes profound lymphoid depletion in endothelin receptor B\u2010 and endothelin 3\u2010null mouse models of Hirschsprung\u2010associated enterocolitis"],"prefix":"10.1002","volume":"45","author":[{"given":"Philip K.","family":"Frykman","sequence":"first","affiliation":[{"name":"Division of Pediatric Surgery and The Pediatric Surgery Laboratory Department of Surgery Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery and The Pediatric Surgery Laboratory Department of Surgery Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery and The Pediatric Surgery Laboratory Department of Surgery Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti","family":"Dhall","sequence":"additional","affiliation":[{"name":"Department of Pathology Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,19]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","article-title":"Stuhtragheit neugeborener infolge dilatationen und hypertrophie des colons","volume":"27","author":"Hirschsprung H.","year":"1887","journal-title":"Jahruch Kinderheikunde"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1710970421"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.10.052"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-197509000-00008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2004.10.014"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(97)90616-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.851"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.031302"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90017-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.2.867"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2009.06.009"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2009.10.035"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.06.006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-010-2787-y"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000069481"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3765"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1309\/RV6E9BMC9954A2WU"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90018-3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90029-C"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-8749(03)00023-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.06.015"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/00313029500169702"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2000.16676"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513818909037731"},{"key":"e_1_2_7_26_1","first-page":"491","article-title":"Involvement of BCL\u20102 in glucocorticoid\u2010induced apoptosis of human pre\u2010B\u2010leukemias","volume":"52","author":"Alnemri E. 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