{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:00:24Z","timestamp":1788872424933,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T00:00:00Z","timestamp":1357776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["FOR-521 (SI861\/1)"],"award-info":[{"award-number":["FOR-521 (SI861\/1)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["GRK-1167 (TP12)"],"award-info":[{"award-number":["GRK-1167 (TP12)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["SFB-854 (TP19)"],"award-info":[{"award-number":["SFB-854 (TP19)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>SIT and LAX, two transmembrane adaptor molecules, cooperatively regulate immune functions and limit autoimmunity.<\/jats:p>\n                  <jats:p>Lymphocyte activation is crucial for the generation of immune responses. In vitro studies have demonstrated that TRAPs are critical regulators of lymphocyte activation. However, more recent in vivo studies have demonstrated that with the exception of LAT, TRAPs, such as SIT, NTAL, and LAX, only minimally affect immune cell functions. Additional studies have suggested that the mild or the apparent lack of a phenotype displayed by most TRAP KO mice may be explained by functional redundancy among this family of adaptors. In fact, it has been shown that the phenotype of NTAL\/LAT or SIT\/TRIM double-deficient mice is more severe than that of the single KOs. Here, we have evaluated whether SIT and the related transmembrane adaptor LAX have overlapping functions by generating SIT\/LAX DKO mice. We show that DKO, in contrast to single KO mice, accumulate large numbers of activated CD4+ T cells in the spleen. Moreover, conventional B cells from DKO mice are hyperproliferative upon CD40 stimulation. Additionally, we found that DKO mice displayed an expansion of the B1 cell pool in the peritoneal cavity, hypergammaglobulinaemia, and an enhanced immune response to the T1-independent antigen, TNP-LPS. Finally, we demonstrate that SIT\/LAX double deficiency resulted in a more pronounced breakdown of peripheral tolerance and the development of autoimmunity characterized by ANAs and renal disease (glomerulonephritis and proteinuria). Collectively, our data indicate that SIT and LAX are important negative regulators of immune responses that functionally cooperate.<\/jats:p>","DOI":"10.1189\/jlb.0312152","type":"journal-article","created":{"date-parts":[[2013,1,11]],"date-time":"2013-01-11T02:09:27Z","timestamp":1357870167000},"page":"353-362","source":"Crossref","is-referenced-by-count":2,"title":["Cooperative immunoregulatory function of the transmembrane adaptor proteins SIT and LAX"],"prefix":"10.1093","volume":"93","author":[{"given":"B\u00f6rge","family":"Arndt","sequence":"first","affiliation":[{"name":"Institutes of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kalinski","sequence":"additional","affiliation":[{"name":"Pathology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Institutes of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Thielitz","sequence":"additional","affiliation":[{"name":"Clinic of Dermatology and Venerology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Roessner","sequence":"additional","affiliation":[{"name":"Pathology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhart","family":"Schraven","sequence":"additional","affiliation":[{"name":"Institutes of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"},{"name":"Department of Immune Control, Helmholtz Centre for Infection Research , Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Simeoni","sequence":"additional","affiliation":[{"name":"Institutes of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,1,10]]},"reference":[{"key":"2023012312530522400_B1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nri1414","article-title":"Transmembrane adaptor proteins: organizers of immunoreceptor signalling","volume":"4","author":"Horejsi","year":"2004","journal-title":"Nat. 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Immunol."},{"key":"2023012312530522400_B3","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1074-7613(00)80032-1","article-title":"Essential role of LAT in T cell development","volume":"10","author":"Zhang","year":"1999","journal-title":"Immunity"},{"key":"2023012312530522400_B4","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.immuni.2006.08.025","article-title":"Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB","volume":"25","author":"Zhu","year":"2006","journal-title":"Immunity"},{"key":"2023012312530522400_B5","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.4049\/jimmunol.174.9.5612","article-title":"Negative regulation of lymphocyte activation by the adaptor protein LAX","volume":"174","author":"Zhu","year":"2005","journal-title":"J. Immunol."},{"key":"2023012312530522400_B6","doi-asserted-by":"crossref","first-page":"18408","DOI":"10.1074\/jbc.M601535200","article-title":"Negative regulation of Fc \u220aRI-mediated signaling and mast cell function by the adaptor protein LAX","volume":"281","author":"Zhu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2023012312530522400_B7","doi-asserted-by":"crossref","first-page":"7557","DOI":"10.1128\/MCB.25.17.7557-7568.2005","article-title":"The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions","volume":"25","author":"Simeoni","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"2023012312530522400_B8","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.4049\/jimmunol.180.3.1634","article-title":"Regulation of T cell homeostasis by the transmembrane adaptor protein SIT","volume":"180","author":"Posevitz","year":"2008","journal-title":"J. Immunol."},{"key":"2023012312530522400_B9","doi-asserted-by":"crossref","first-page":"e23761","DOI":"10.1371\/journal.pone.0023761","article-title":"The transmembrane adaptor protein SIT inhibits TCR-mediated signaling","volume":"6","author":"Arndt","year":"2011","journal-title":"PLoS One"},{"key":"2023012312530522400_B10","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1128\/MCB.26.9.3639-3648.2006","article-title":"Normal T-cell development and immune functions in TRIM-deficient mice","volume":"26","author":"Kolsch","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"2023012312530522400_B11","doi-asserted-by":"crossref","first-page":"8486","DOI":"10.1128\/MCB.25.19.8486-8495.2005","article-title":"Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development","volume":"25","author":"Xu","year":"2005","journal-title":"Mol. Cell. 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