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- Publisher Website: 10.1073/pnas.1014304108
- Scopus: eid_2-s2.0-79955027961
- PMID: 21444811
- WOS: WOS:000289413600057
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Conference Paper: Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes
Title | Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes |
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Authors | |
Keywords | Lysosomal storage disorder Transcriptional control of iNKT lineage Invariant natural killer T-cell development Inkt cell selection |
Issue Date | 2011 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2011, v. 108, n. 15, p. 6211-6216 How to Cite? |
Abstract | Invariant natural killer T cells (iNKT cells) are innate-like T cells important in immune regulation, antimicrobial protection, and anti-tumor responses. They express semi-invariant T cell receptors, which recognize glycolipid antigens. Their positive selection is mediated by double-positive (DP) thymocytes, which present glycolipid self-antigens through the noncanonical MHC class I-like molecule CD1d. Here we provide genetic and biochemical evidence that removal of the transcription factor Bcl11b in DP thymocytes leads to an early block in iNKT cell development, caused by both iNKT cell extrinsic and intrinsic defects. Specifically, Bcl11bdeficient DP thymocytes failed to support Bcl11b-sufficient iNKT precursor development due to defective glycolipid self-antigen presentation, and showed enlarged lysosomes and accumulation of glycosphingolipids. Expression of genes encoding lysosomal proteins with roles in sphingolipid metabolism and glycolipid presentation was found to be altered in Bcl11b-deficient DP thymocytes. These include cathepsins and Niemann-Pick disease type A, B, and C genes. Thus, Bcl11b plays a central role in presentation of glycolipid self-antigens by DP thymocytes, and regulates directly or indirectly expression of lysosomal genes, exerting a critical extrinsic role in development of iNKT lineage, in addition to the intrinsic role in iNKT precursors. These studies demonstrate a unique and previously undescribed role of Bcl11b in DP thymocytes, in addition to the critical function in positive selection of conventional CD4 and CD8 single-positive thymocytes. |
Persistent Identifier | http://hdl.handle.net/10722/249048 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Albu, Diana I. | - |
dc.contributor.author | VanValkenburgh, Jeffrey | - |
dc.contributor.author | Morin, Nicole | - |
dc.contributor.author | Califano, Danielle | - |
dc.contributor.author | Jenkins, Nancy A. | - |
dc.contributor.author | Copeland, Neal G. | - |
dc.contributor.author | Liu, Pentao | - |
dc.contributor.author | Avram, Dorina | - |
dc.date.accessioned | 2017-10-27T05:58:58Z | - |
dc.date.available | 2017-10-27T05:58:58Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2011, v. 108, n. 15, p. 6211-6216 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/249048 | - |
dc.description.abstract | Invariant natural killer T cells (iNKT cells) are innate-like T cells important in immune regulation, antimicrobial protection, and anti-tumor responses. They express semi-invariant T cell receptors, which recognize glycolipid antigens. Their positive selection is mediated by double-positive (DP) thymocytes, which present glycolipid self-antigens through the noncanonical MHC class I-like molecule CD1d. Here we provide genetic and biochemical evidence that removal of the transcription factor Bcl11b in DP thymocytes leads to an early block in iNKT cell development, caused by both iNKT cell extrinsic and intrinsic defects. Specifically, Bcl11bdeficient DP thymocytes failed to support Bcl11b-sufficient iNKT precursor development due to defective glycolipid self-antigen presentation, and showed enlarged lysosomes and accumulation of glycosphingolipids. Expression of genes encoding lysosomal proteins with roles in sphingolipid metabolism and glycolipid presentation was found to be altered in Bcl11b-deficient DP thymocytes. These include cathepsins and Niemann-Pick disease type A, B, and C genes. Thus, Bcl11b plays a central role in presentation of glycolipid self-antigens by DP thymocytes, and regulates directly or indirectly expression of lysosomal genes, exerting a critical extrinsic role in development of iNKT lineage, in addition to the intrinsic role in iNKT precursors. These studies demonstrate a unique and previously undescribed role of Bcl11b in DP thymocytes, in addition to the critical function in positive selection of conventional CD4 and CD8 single-positive thymocytes. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | Lysosomal storage disorder | - |
dc.subject | Transcriptional control of iNKT lineage | - |
dc.subject | Invariant natural killer T-cell development | - |
dc.subject | Inkt cell selection | - |
dc.title | Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes | - |
dc.type | Conference_Paper | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1014304108 | - |
dc.identifier.pmid | 21444811 | - |
dc.identifier.scopus | eid_2-s2.0-79955027961 | - |
dc.identifier.volume | 108 | - |
dc.identifier.issue | 15 | - |
dc.identifier.spage | 6211 | - |
dc.identifier.epage | 6216 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000289413600057 | - |
dc.identifier.issnl | 0027-8424 | - |