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ZBTB7B (Th-POK) regulates the development of IL-17 -producing-CD1d-restricted mouse NKT cells

Enders, Anselm; Stankovic, Sanda; Teh, Charis; Uldrich, Adam P; Yabas, Mehmet; Juelich, Torsten; Altin, John A.; Frankenreiter, Sandra; Bergmann, Hannes; Roots, Carla M.; Kyparissoudis, Konstantinos; Goodnow, Chris C.; Godfrey, Dale I.

Description

CD1d-dependent NKT cells represent a heterogeneous family of effector T cells including CD4+CD8- and CD4-CD8- subsets that respond to glycolipid Ags with rapid and potent cytokine production. NKT cell development is regulated by a unique combination of factors, however very little is known about factors that control the development of NKT subsets. In this study, we analyze a novel mouse strain (helpless) with a mis-sense mutation in the BTB-POZ domain of ZBTB7B and demonstrate that this...[Show more]

dc.contributor.authorEnders, Anselm
dc.contributor.authorStankovic, Sanda
dc.contributor.authorTeh, Charis
dc.contributor.authorUldrich, Adam P
dc.contributor.authorYabas, Mehmet
dc.contributor.authorJuelich, Torsten
dc.contributor.authorAltin, John A.
dc.contributor.authorFrankenreiter, Sandra
dc.contributor.authorBergmann, Hannes
dc.contributor.authorRoots, Carla M.
dc.contributor.authorKyparissoudis, Konstantinos
dc.contributor.authorGoodnow, Chris C.
dc.contributor.authorGodfrey, Dale I.
dc.date.accessioned2013-09-04T02:00:19Z
dc.date.available2013-09-04T02:00:19Z
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.urihttp://hdl.handle.net/1885/10400
dc.description.abstractCD1d-dependent NKT cells represent a heterogeneous family of effector T cells including CD4+CD8- and CD4-CD8- subsets that respond to glycolipid Ags with rapid and potent cytokine production. NKT cell development is regulated by a unique combination of factors, however very little is known about factors that control the development of NKT subsets. In this study, we analyze a novel mouse strain (helpless) with a mis-sense mutation in the BTB-POZ domain of ZBTB7B and demonstrate that this mutation has dramatic, intrinsic effects on development of NKT cell subsets. Although NKT cell numbers are similar in Zbtb7b mutant mice, these cells are hyperproliferative and most lack CD4 and instead express CD8. Moreover, the majority of ZBTB7B mutant NKT cells in the thymus are retinoic acid-related orphan receptor γt positive, and a high frequency produce IL-17 while very few produce IFN-γ or other cytokines, sharply contrasting the profile of normal NKT cells. Mice heterozygous for the helpless mutation also have reduced numbers of CD4+ NKT cells and increased production of IL-17 without an increase in CD8+ cells, suggesting that ZBTB7B acts at multiple stages of NKT cell development. These results reveal ZBTB7B as a critical factor genetically predetermining the balance of effector subsets within the NKT cell population.
dc.description.sponsorshipNHMRC (National Health and Medical Research Council of Australia)
dc.format10 + 5 pages
dc.publisherAmerican Association of Immunologists
dc.rightshttp://www.sherpa.ac.uk/romeo/issn/0022-1767/ Author may archive post-print but only on a personal website, not on an Institutional Repository. Pre-print archiving unclear. Author cannot archive publisher's version/PDF but may use, if part of a thesis/dissertation, within a thesis repository. Pre-print archiving may be considered prior publication. Set statement must accompany article (see policy link). Must link to publisher version - from SHERPA/RoMEO site (as at 3/9/13)
dc.sourceJournal of Immunology 189.11 (2012): 5240-5249
dc.source.urihttp://www.jimmunol.org/content/189/11/5240
dc.subjectNKT cells
dc.subjectTh-POK
dc.subjectThPOK
dc.subjectZbtb7b
dc.subjectIL-17
dc.titleZBTB7B (Th-POK) regulates the development of IL-17 -producing-CD1d-restricted mouse NKT cells
dc.typeJournal article
local.description.notesThis document is not available from institutional repositories due to publisher-imposed restrictions.
local.identifier.citationvolume189
dc.date.issued2012-10-26
local.identifier.absfor060100 - BIOCHEMISTRY AND CELL BIOLOGY
local.identifier.absfor060406 - Genetic Immunology
local.identifier.absfor110700 - IMMUNOLOGY
local.identifier.ariespublicationf5625xPUB1997
local.publisher.urlhttp://www.jimmunol.org
local.type.statusPublished Version
local.contributor.affiliationEnders, Anselm, ANU, John Curtin School of Medical Research, Department of Immunology, Ramaciotti Immunization Genomics Laboratory
local.contributor.affiliationStankovic, Sanda, University of Melbourne, Department of Microbiology and Immunology
local.contributor.affiliationTeh, Charis, ANU, John Curtin School of Medical Research, Department of Immunology, Ramaciotti Immunization Genomics Laboratory
local.contributor.affiliationUldrich, Adam P., University of Melbourne, Department of Microbiology and Immunology
local.contributor.affiliationYabas, Mehmet, ANU, John Curtin School of Medical Research, Department of Immunology, Ramaciotti Immunization Genomics Laboratory
local.contributor.affiliationJuelich, Torsten, ANU, John Curtin School of Medical Research, Department of Immunology
local.contributor.affiliationAltin, John A., ANU, John Curtin School of Medical Research, Department of Immunology
local.contributor.affiliationFrankenreiter, Sandra, ANU, John Curtin School of Medical Research, Department of Immunology, Ramaciotti Immunization Genomics Laboratory
local.contributor.affiliationBergmann, Hannes, ANU, John Curtin School of Medical Research, Department of Immunology, Ramaciotti Immunization Genomics Laboratory
local.contributor.affiliationRoots, Carla M., ANU, John Curtin School of Medical Research, Department of Immunology; Australian Phenomics Facility
local.contributor.affiliationKyparissoudis, Konstantinos, University of Melbourne, Department of Microbiology and Immunology
local.contributor.affiliationGoodnow, Chris C., ANU, John Curtin School of Medical Research, Department of Immunology; Australian Phenomics Facility
local.contributor.affiliationGodfrey, Dale I., University of Melbourne, Department of Microbiology and Immunology
dc.relationhttp://purl.org/au-research/grants/nhmrc/1009190
dc.relationhttp://purl.org/au-research/grants/nhmrc/1035858
dc.relationhttp://purl.org/au-research/grants/nhmrc/1020770
dc.relationhttp://purl.org/au-research/grants/nhmrc/585490
dc.relationnih ai054523
dc.relationramaciotti foundation major initiative award 2007
local.bibliographicCitation.issue11
local.bibliographicCitation.startpage5240
local.bibliographicCitation.lastpage5249
local.identifier.doi10.4049/jimmunol.1201486
local.identifier.absseo920108 - Immune System and Allergy
dc.date.updated2015-12-10T11:31:29Z
local.identifier.scopusID2-s2.0-84869767226
local.identifier.thomsonID000311287600020
CollectionsANU Research Publications

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