{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:38:06Z","timestamp":1790386686318,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,6,19]]},"abstract":"<jats:p>\n                    Inherited deficiency of acid \u03b2-glucosidase (GCase) due to biallelic mutations in the\n                    <jats:italic>GBA<\/jats:italic>\n                    (glucosidase, \u03b2, acid) gene causes the classic manifestations of Gaucher disease (GD) involving the viscera, the skeleton, and the lungs. Clinical observations point to immune defects in GD beyond the accumulation of activated macrophages engorged with lysosomal glucosylceramide. Here, we show a plethora of immune cell aberrations in mice in which the\n                    <jats:italic>GBA<\/jats:italic>\n                    gene is deleted conditionally in hematopoietic stem cells (HSCs). The thymus exhibited the earliest and most striking alterations reminiscent of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes. These changes correlated strongly with disease severity. In contrast to the profound defects in the thymus, there were only limited cellular defects in peripheral lymphoid organs, mainly restricted to mice with severe disease. The cellular changes in GCase deficiency were accompanied by elevated T-helper (Th)1 and Th2 cytokines that also tracked with disease severity. Finally, the proliferation of GCase-deficient HSCs was inhibited significantly by both GL1 and Lyso-GL1, suggesting that the \u201csupply\u201d of early thymic progenitors from bone marrow may, in fact, be reduced in\n                    <jats:italic>GBA<\/jats:italic>\n                    deficiency. The results not only point to a fundamental role for\n                    <jats:italic>GBA<\/jats:italic>\n                    in immune regulation but also suggest that\n                    <jats:italic>GBA<\/jats:italic>\n                    mutations in GD may cause widespread immune dysregulation through the accumulation of substrates.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1200941109","type":"journal-article","created":{"date-parts":[[2012,6,5]],"date-time":"2012-06-05T10:05:21Z","timestamp":1338890721000},"page":"10018-10023","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":75,"title":["Gaucher disease gene\n                    <i>GBA<\/i>\n                    functions in immune regulation"],"prefix":"10.1073","volume":"109","author":[{"given":"Jun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Halene","sequence":"additional","affiliation":[{"name":"Section of Hematology, Department of Medicine, and Yale Comprehensive Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameel","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajahat Z.","family":"Mehal","sequence":"additional","affiliation":[{"name":"Section of Digestive Diseases, Department of Medicine; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Lien","family":"Chuang","sequence":"additional","affiliation":[{"name":"Genzyme Sanofi, Framingham, MA 01701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanpat","family":"Jain","sequence":"additional","affiliation":[{"name":"Section of Digestive Diseases, Department of Medicine; and"},{"name":"Department of Pathology, Yale University School of Medicine, New Haven, CT 06520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Yuen","sequence":"additional","affiliation":[{"name":"Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mone","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod K.","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"},{"name":"Section of Digestive Diseases, Department of Medicine; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,6,4]]},"reference":[{"key":"e_1_3_3_1_2","unstructured":"GA Grabowski GA Petsko EH Kolodny Gaucher Disease. 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