{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:55:16Z","timestamp":1753869316341,"version":"3.41.2"},"reference-count":69,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI\/19K17874"],"award-info":[{"award-number":["KAKENHI\/19K17874"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Allogeneic hematopoietic stem cell transplantation (aHSCT) is a curative treatment for hematopoietic malignancies. Graft\u2010versus\u2010host disease (GVHD) is a major complication of aHSCT. After transplantation, the balance of immune conditions, such as proinflammatory cytokine level and T\u2010cell subset count, influences GVHD magnitude. Lenalidomide (LEN) is an immunomodulatory drug used for treating several hematological malignancies such as multiple myeloma, adult T\u2010cell lymphoma\/leukemia, and follicular lymphoma. However, the impact of LEN on immune responses after aHSCT has not been elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the lymphocyte composition in na\u00efve mice treated with LEN. Subsequently, we treated host mice with LEN, soon after aHSCT, and analyzed GVHD severity as well as the composition and characteristics of lymphocytes associated with GVHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using a mouse model, we demonstrated the beneficial effects of LEN for treating acute GVHD. Although natural killer cells were slightly increased by LEN, it did not significantly change T\u2010cell proliferation and the balance of the T\u2010cell subset in na\u00efve mice. LEN did not modulate the suppressive function of regulatory T cells (Tregs). Unexpectedly, LEN prevented severe GVHD in a mouse acute GVHD model. Donor\u2010derived lymphocytes were more numerous in host mice treated with LEN than in host mice treated with vehicle. Lymphocyte infiltration of the gastrointestinal tract in host mice treated with LEN was less severe compared to that in host mice treated with vehicle. The percentage of LPAM\u20101 (\u03b1<jats:sub>4<\/jats:sub>\u03b2<jats:sub>7<\/jats:sub>\u2010integrin)\u2010expressing Foxp3<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells was significantly lower in host mice treated with LEN than in host mice treated with vehicle, whereas that of LPAM\u20101\u2010expressing Tregs was comparable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>LEN may be useful as a prophylactic agent for acute GVHD\u2010induced mortality through the inhibition of lymphocyte migration to the gastrointestinal tract. Our data show the effect of LEN on immune responses early after aHSCT\u00a0and suggest that cereblon, a molecular target of LEN, may be a therapeutic target for preventing acute GVHD\u2010induced mortality.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.688","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T06:51:04Z","timestamp":1661842264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Early administration of lenalidomide after allogeneic hematopoietic stem cell transplantation suppresses graft\u2010versus\u2010host disease by inhibiting T\u2010cell migration to the gastrointestinal tract"],"prefix":"10.1002","volume":"10","author":[{"given":"Yukie","family":"Tsubokura","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine Kansai Medical University  Hirakata City Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine Kansai Medical University  Hirakata City Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6007-6264","authenticated-orcid":false,"given":"Atsushi","family":"Satake","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine Kansai Medical University  Hirakata City Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaro","family":"Nasa","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine Kansai Medical University  Hirakata City Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryohei","family":"Tsuji","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine Kansai Medical University  Hirakata City Osaka 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