{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:50:58Z","timestamp":1783075858572,"version":"3.54.6"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,1,17]],"date-time":"2016-01-17T00:00:00Z","timestamp":1452988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NCL-Foundation (Hamburg), Novartis (Basel), Interdisciplinary Centre for Clinical Research (IZKF) of the University of Wuerzburg, and local funds of the University Hospital of Wuerzburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>CLN diseases are mostly fatal lysosomal storage diseases that lead to neurodegeneration in the CNS. We have previously shown that CD8+ T\u2010lymphocytes contribute to axonal perturbation and neuron loss in the CNS of <jats:italic>Ppt1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice, a model of CLN1 disease. We now investigated the role of the inflammation\u2010related cell adhesion molecule sialoadhesin (Sn) in <jats:italic>Ppt1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and <jats:italic>Cln3<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice, a model of the most frequent form, CLN3 disease. Microglia\/macrophages in the CNS of both models showed an upregulation of Sn and markers for proinflammatory M1 polarization and antigen presentation. Sn+ microglia\/macrophages associated with SMI32+ axonal spheroids and CD8+ T\u2010lymphocytes. To analyze their pathogenic impact, we crossbred both models with <jats:italic>Sn<\/jats:italic>\u2010deficient mice and scored axonal degeneration and neuronal integrity using immunohistochemistry, electron microscopy and optical coherence tomography. Degenerative alterations in the retinotectal pathway of <jats:italic>Ppt1<jats:sup>\u2212\/\u2212<\/jats:sup>Sn<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and <jats:italic>Cln3<jats:sup>\u2212\/\u2212<\/jats:sup>Sn<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice were significantly reduced. <jats:italic>Ppt1<jats:sup>\u2212\/\u2212<\/jats:sup>Sn<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice also showed a substantially improved clinical phenotype and extended lifespan, attenuated numbers of M1\u2010polarized microglia\/macrophages and reduced expression levels of proinflammatory cytokines. This was accompanied by an increased frequency of CD8+CD122+ T\u2010lymphocytes in the CNS of <jats:italic>Ppt1<jats:sup>\u2212\/\u2212<\/jats:sup>Sn<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice, the regulatory phenotype of which was demonstrated by impaired survival of CD8+CD122\u2212 effector T\u2010lymphocytes in co\u2010culture experiments. We show for the first time that increased Sn expression on microglia\/macrophages contributes to neural perturbation in two distinct models of CLN disease. Our data also indicate that a rarely described CD8+CD122+ T\u2010cell population can regulate the corresponding diseases. These studies provide insights into CLN pathogenesis and may guide in designing immuno\u2010regulatory treatment strategies. 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