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However, its contribution in the setting of chronic systemic autoimmunity has not been investigated. We made use of the <jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> autoimmune model, generating <jats:italic>Cd53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, and compared trafficking of immune cells into secondary lymphoid organs and systemic autoimmune disease development with mice lacking either gene alone. Consistent with previous observations, absence of CD53 led to reduced LN cellularity via reductions in both B and T cells, a phenotype also observed in <jats:italic>Cd53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. In some settings, <jats:italic>Cd53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> lymphocytes showed greater loss of surface L\u2010selectin and CD69 upregulation above that imparted by Lyn deficiency alone, indicating that absence of these two proteins can mediate additive effects in the immune system. Conversely, prototypical effects of Lyn deficiency including splenomegaly, plasma cell expansion, elevated serum immunoglobulin M and anti\u2010nuclear antibodies were unaffected by CD53 deficiency. Furthermore, while <jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice developed glomerular injury and showed elevated glomerular neutrophil retention above than that in wild\u2010type mice, absence of CD53 in <jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice did not alter these responses. Together, these findings demonstrate that while tetraspanin CD53 promotes lymphocyte trafficking into LNs independent of Lyn, it does not make an important contribution to development of autoimmunity, plasma cell dysfunction or glomerular injury in the <jats:italic>Lyn<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> model of systemic autoimmunity.<\/jats:p>","DOI":"10.1111\/imcb.12501","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T06:02:13Z","timestamp":1631512933000},"page":"1053-1066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tetraspanin CD53 modulates lymphocyte trafficking but not systemic autoimmunity in Lyn\u2010deficient mice"],"prefix":"10.1111","volume":"99","author":[{"given":"Louisa","family":"Yeung","sequence":"first","affiliation":[{"name":"Centre for Inflammatory Diseases Department of Medicine Monash Medical Centre Monash University Clayton VIC 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