{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T02:13:13Z","timestamp":1772071993355,"version":"3.50.1"},"reference-count":100,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gaucher disease is a lysosomal storage disease, which happens due to mutations in GBA1\/Gba1 that encodes the enzyme termed as lysosomal acid \u03b2-glucosidase. The major function of this enzyme is to catalyze glucosylceramide (GC) into glucose and ceramide. The deficiency of this enzyme and resultant abnormal accumulation of GC cause altered function of several of the innate and adaptive immune cells. For example, augmented infiltration of T cells contributes to the increased production of pro-inflammatory cytokines, (e.g., IFN\u03b3, TNF\u03b1, IL6, IL12p40, IL12p70, IL23, and IL17A\/F). This leads to tissue damage in a genetic mouse model (Gba19V\/\u2212) of Gaucher disease. The cellular mechanism(s) by which increased tissue infiltration of T cells occurs in this disease is not fully understood. Here, we delineate role of the CXCR3 receptor and its exogenous C-X-C motif chemokine ligand 9 (CXCL9) in induction of increased tissue recruitment of CD4+ T and CD8+ T cells in Gaucher disease. Intracellular FACS staining of macrophages (M\u03d5s) and dendritic cells (DCs) from Gba19V\/\u2212 mice showed elevated production of CXCL9. Purified CD4+ T cells and the CD8+ T cells from Gba19V\/\u2212 mice showed increased expression of CXCR3. Ex vivo and in vivo chemotaxis experiments showed CXCL9 involvement in the recruitment of Gba19V\/\u2212 T cells. Furthermore, antibody blockade of the CXCL9 receptor (CXCR3) on T cells caused marked reduction in CXCL9- mediated chemotaxis of T cells in Gba19V\/\u2212 mice. These data implicate abnormalities of the CXCL9-CXCR3 axis leading to enhanced tissue recruitment of T cells in Gaucher disease. Such results provide a rationale for blockade of the CXCL9\/CXCR3 axis as potential new therapeutic targets for the treatment of inflammation in Gaucher disease.<\/jats:p>","DOI":"10.3390\/ijms222312712","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"12712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Albert Frank","family":"Magnusen","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reena","family":"Rani","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5412-0986","authenticated-orcid":false,"given":"Mary Ashley","family":"McKay","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby Loraine","family":"Hatton","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsitsi Carol","family":"Nyamajenjere","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Nii Aryee","family":"Magnusen","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-3178","authenticated-orcid":false,"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"},{"name":"Department of Pediatrics and Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory Alex","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry and Microbiology, Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-830X","authenticated-orcid":false,"given":"Manoj Kumar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1038\/s41598-021-82296-z","article-title":"Predicting the probability of Gaucher disease in subjects with splenomegaly and thrombocytopenia","volume":"11","author":"Motta","year":"2021","journal-title":"Sci. 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