{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:51:08Z","timestamp":1791294668300,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NKT17 cells represent a functional subset of V\u03b114 invariant NKT (iNKT) cells with important effector functions in infections and autoimmune diseases. The mechanisms that drive NKT17 cell differentiation in the thymus are still largely unknown. The percentage of NKT17 cells has a high variability between murine strains due to differential thymic differentiation. For example, the NOD strain carries a high percentage and absolute numbers of NKT17 cells compared with other strains. In this study, we used the NOD mouse model to analyze what regulates NKT17 cell frequency in the thymus and peripheral lymphoid organs. In accordance with previous studies showing that the zinc finger transcription factor Th-POK is a key negative regulator of thymic NKT17 cell differentiation in the thymus, our data indicate that excessive NKT17 cell frequency in NOD mice correlates with defective Th-POK expression by thymic V\u03b114iNKT cells. Moreover, we found that Th-POK expression is under epigenetic regulation mediated by microRNA-133b whose expression is reduced in V\u03b114iNKT cells of NOD mice. We also demonstrated in a conditional knockout model of dendritic cell (DC) depletion (CD11cCreXDTA.B6 and CD11cCreRosa26DTA.NOD mice) that DCs play a crucial role in regulating V\u03b114iNKT cell maturation and their acquisition of an NKT17 cytokine secretion phenotype in the thymus. Overall, our data show that mechanisms regulating NKT17 cell differentiation are unique and completely different from those of V\u03b114iNKT cells. Specifically, we found that epigenetic regulation through microRNA-133b\u2013regulated Th-POK expression and signals provided by DCs are fundamental for thymic NKT17 cell differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.1502238","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T02:08:21Z","timestamp":1473300501000},"page":"3271-3280","source":"Crossref","is-referenced-by-count":16,"title":["MicroRNA-133b Regulation of Th-POK Expression and Dendritic Cell Signals Affect NKT17 Cell Differentiation in the Thymus"],"prefix":"10.1093","volume":"197","author":[{"given":"Caterina","family":"Di Pietro","sequence":"first","affiliation":[{"name":"Experimental Diabetes Unit\u2013Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7480-5720","authenticated-orcid":false,"given":"Lorena","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Experimental Diabetes Unit\u2013Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cosorich","sequence":"additional","affiliation":[{"name":"Experimental Diabetes Unit\u2013Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6803-8377","authenticated-orcid":false,"given":"Chiara","family":"Sorini","sequence":"additional","affiliation":[{"name":"Experimental Diabetes Unit\u2013Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Fedeli","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Institute for Research,\u00a0Hospitalization, and Health Care, San Raffaele Scientific Institute , 20132 Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6080-5351","authenticated-orcid":false,"given":"Marika","family":"Falcone","sequence":"additional","affiliation":[{"name":"Experimental Diabetes Unit\u2013Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,10,15]]},"reference":[{"key":"2025030617553502200_r1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1146\/annurev.immunol.23.021704.115742","article-title":"Toward an understanding of NKT cell biology: progress and paradoxes","volume":"23","author":"Kronenberg","year":"2005","journal-title":"Annu. 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