{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:18:51Z","timestamp":1747185531464,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130106"],"award-info":[{"award-number":["82130106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intestinal intraepithelial lymphocytes (IELs) play a crucial role in host defence against pathogens in the intestinal mucosa. The development of intestinal IELs is distinct from peripheral T lymphocytes and remains elusive. Fas\u2010associated protein with death domain (FADD) is important for T cell development in the thymus. Here we describe a novel function of FADD in the IEL development. FADD (S191A), a mouse FADD mutant at Ser191 to Ala mimicking constitutively unphosphorylated FADD, promoted a rapid expansion of TCR\u03b1\u03b2<jats:sup>+<\/jats:sup> IELs, not TCR\u03b3\u03b4<jats:sup>+<\/jats:sup> IELs. Mechanism investigation indicated that the dephosphorylation of FADD was required for cell activation mainly in TCR\u03b1\u03b2<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells. Consistently, FADD (S191A) as dephosphorylated FADD led to a high NF\u2010\u03baB activation in the TCR\u2010dependent cell expansion. In addition, The FADD (S191A)\u2010induced abnormal IEL populations resulted in the increased incidence and severity of colitis in mice. In summary, FADD signalling is involved in the intestinal IEL development and might be a regulator for intestinal mucosal homeostasis.<\/jats:p>","DOI":"10.1111\/imm.13533","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T17:14:56Z","timestamp":1656263696000},"page":"233-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The dephosphorylation of <scp>FADD<\/scp> at <scp>S191<\/scp> induces an excessive expansion of <scp>TCR\u03b1\u03b2<\/scp><sup>+<\/sup><scp>IELs<\/scp> in the intestinal mucosa"],"prefix":"10.1111","volume":"167","author":[{"given":"Xuerui","family":"Zhang","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"},{"name":"School of Pharmaceutical Sciences Shandong First Medical University  Taian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banghui","family":"Zhu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahong","family":"Xu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuheng","family":"Han","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3733-8104","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7962-0402","authenticated-orcid":false,"given":"Zichun","family":"Hua","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences Nanjing University  Nanjing China"},{"name":"School of Biopharmacy China Pharmaceutical University  Nanjing China"},{"name":"Changzhou High\u2010Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc.  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.11.003"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20010798"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.47"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0013-7"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-4016-y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-016-0519-x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0016-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304066"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.55"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1639-3"},{"issue":"11","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.4049\/jimmunol.154.11.5611","article-title":"Differences in intraepithelial lymphocyte T cell subsets isolated from murine small versus large intestine","volume":"154","author":"Beagley KW","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90071-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.154"},{"key":"e_1_2_11_15_1","article-title":"Functional complementation between FADD and RIP1 in embryos and lymphocytes","volume":"471","author":"Zhang H, Zhou X, McQuade T, Li J, Chan FK, Zhang JK","year":"2011","journal-title":"Nature"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00600-07"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/32681"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103838200"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3033"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.198"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00083-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540400008929"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.1.187"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.018"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.2.471"},{"issue":"6","key":"e_1_2_11_26_1","first-page":"1347","article-title":"Effects of protein deficiency and natural intestinal infection with Giardia lamblia on jejunal intraepithelial lymphocytes in rats of different ages","volume":"27","author":"Rodrigues MA","year":"1994","journal-title":"Braz J Med Biol Res"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20420"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1995.tb03645.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.014"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00480.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.077"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11370"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01065"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040557"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.10.019"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3751"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.004"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092316"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0831037100"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5825"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830200523"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2106"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13533","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.13533","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13533","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T10:54:15Z","timestamp":1692615255000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/imm.13533"],"URL":"https:\/\/doi.org\/10.1111\/imm.13533","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"type":"print","value":"0019-2805"},{"type":"electronic","value":"1365-2567"}],"subject":[],"published":{"date-parts":[[2022,7,12]]},"assertion":[{"value":"2021-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}