{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T08:11:05Z","timestamp":1784103065646,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T00:00:00Z","timestamp":1398988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>The intracellular adaptor Lnk (also known as SH2B3) regulates cytokine signals that control lymphohematopoiesis, and <jats:italic>Lnk<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice have expanded B\u2010cell, megakaryocyte, and hematopoietic stem\u2010cell populations. Moreover, mutations in the <jats:italic>LNK<\/jats:italic> gene are found in patients with myeloproliferative disease, whereas <jats:italic>LNK<\/jats:italic> polymorphisms have recently been associated with inflammatory and autoimmune diseases, including celiac disease. Here, we describe a previously unrecognized function of Lnk in the control of inflammatory CD8<jats:sup>+<\/jats:sup> T\u2010cell proliferation and in intestinal homeostasis. Mature T\u00a0cells from newly generated <jats:italic>Lnk<\/jats:italic>\u2013Venus reporter mice had low but substantial expression of <jats:italic>Lnk<\/jats:italic>, whereas <jats:italic>Lnk<\/jats:italic> expression was downregulated during homeostatic T\u2010cell proliferation under lymphopenic conditions. The numbers of CD44<jats:sup>hi<\/jats:sup>IFN\u2010\u03b3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> effector or memory T\u00a0cells were found to be increased in <jats:italic>Lnk<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice, which also exhibited shortening of villi in the small intestine. <jats:italic>Lnk<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> CD8<jats:sup>+<\/jats:sup> T\u00a0cells survived longer in response to stimulation with IL\u201015 and proliferated even in nonlymphopenic hosts. Transfer of <jats:italic>Lnk<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> CD8<jats:sup>+<\/jats:sup> T\u00a0cells together with WT CD4<jats:sup>+<\/jats:sup> T\u00a0cells into <jats:italic>Rag2<\/jats:italic>\u2010deficient mice recapitulated a sign of villous abnormality. Our results reveal a link between Lnk and immune cell\u2010mediated intestinal tissue destruction.<\/jats:p>","DOI":"10.1002\/eji.201343883","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T18:27:40Z","timestamp":1392661660000},"page":"1622-1632","source":"Crossref","is-referenced-by-count":25,"title":["Lnk prevents inflammatory CD8<sup>+<\/sup> T\u2010cell proliferation and contributes to intestinal homeostasis"],"prefix":"10.1002","volume":"44","author":[{"given":"Hiroko","family":"Katayama","sequence":"first","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taizo","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Anraku","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Iseki","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ikutani","sequence":"additional","affiliation":[{"name":"Department of Immunobiology and Pharmacological Genetics Graduate School of Medicine and Pharmaceutical Science for Research University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics Center for Experimental Medicine and Systems Biology The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Takatsu","sequence":"additional","affiliation":[{"name":"Department of Immunobiology and Pharmacological Genetics Graduate School of Medicine and Pharmaceutical Science for Research University of Toyama  Toyama Japan"},{"name":"Toyama Prefectural Institute for Pharmaceutical Research  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takaki","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation Research Institute National Center for Global Health and Medicine  Ichikawa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00060-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5199"},{"key":"e_1_2_7_4_1","first-page":"1","article-title":"Lnk adaptor: novel negative regulator of B cell lymphopoiesis","volume":"85","author":"Rudd C. 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