Show simple item record

dc.contributor.authorYin, Catherine C.
dc.contributor.authorCho, Ok Hyun
dc.contributor.authorSylvia, Katelyn E.
dc.contributor.authorNarayan, Kavitha
dc.contributor.authorPrince, Amanda L.
dc.contributor.authorEvans, John W.
dc.contributor.authorKang, Joonsoo
dc.contributor.authorBerg, Leslie J.
dc.date2022-08-11T08:08:22.000
dc.date.accessioned2022-08-23T15:52:38Z
dc.date.available2022-08-23T15:52:38Z
dc.date.issued2013-03-15
dc.date.submitted2013-07-08
dc.identifier.citation<p>J Immunol. 2013 Mar 15;190(6):2659-69. doi: 10.4049/jimmunol.1202531. <a href="http://dx.doi.org/10.4049/jimmunol.1202531">Link to article on publisher's site</a></p>
dc.identifier.issn0022-1767 (Linking)
dc.identifier.doi10.4049/jimmunol.1202531
dc.identifier.pmid23378428
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29185
dc.description<p>Co-author Amanda Prince is a student in the Immunology and Virology Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.</p>
dc.description.abstractThe Tec family tyrosine kinase, Itk, regulates signaling downstream of the TCR. The absence of Itk in CD4(+) T cells results in impaired Th2 responses along with defects in maturation, cytokine production, and survival of iNKT cells. Paradoxically, Itk(-/-) mice have spontaneously elevated serum IgE levels, resulting from an expansion of the Vgamma1.1(+)Vdelta6.3(+) subset of gammadelta T cells, known as gammadelta NKT cells. Comparisons between gammadelta NKT cells and alphabeta iNKT cells showed convergence in the pattern of cell surface marker expression, cytokine profiles, and gene expression, suggesting that these two subsets of NKT cells undergo similar differentiation programs. Hepatic gammadelta NKT cells have an invariant TCR and are derived predominantly from fetal progenitors that expand in the thymus during the first weeks of life. The adult thymus contains these invariant gammadelta NKT cells plus a heterogeneous population of Vgamma1.1(+)Vdelta6.3(+) T cells with diverse CDR3 sequences. This latter population, normally excluded from the liver, escapes the thymus and homes to the liver when Itk is absent. In addition, Itk(-/-) gammadelta NKT cells persistently express high levels of Zbtb16 (PLZF) and Il4, genes that are normally downregulated in the most mature subsets of NKT cells. These data indicate that Itk signaling is required to prevent the expansion of gammadelta NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23378428&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594397/
dc.subjectAnimals
dc.subjectCell Aging
dc.subjectCell Differentiation
dc.subjectCell Migration Inhibition
dc.subjectCell Movement
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectNatural Killer T-Cells
dc.subjectProtein-Tyrosine Kinases
dc.subjectReceptors, Antigen, T-Cell, gamma-delta
dc.subjectThymus Gland
dc.subjectUMCCTS funding
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectImmunity
dc.subjectImmunology and Infectious Disease
dc.titleThe Tec kinase ITK regulates thymic expansion, emigration, and maturation of gammadelta NKT cells
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume190
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/141
dc.identifier.contextkey4295161
html.description.abstract<p>The Tec family tyrosine kinase, Itk, regulates signaling downstream of the TCR. The absence of Itk in CD4(+) T cells results in impaired Th2 responses along with defects in maturation, cytokine production, and survival of iNKT cells. Paradoxically, Itk(-/-) mice have spontaneously elevated serum IgE levels, resulting from an expansion of the Vgamma1.1(+)Vdelta6.3(+) subset of gammadelta T cells, known as gammadelta NKT cells. Comparisons between gammadelta NKT cells and alphabeta iNKT cells showed convergence in the pattern of cell surface marker expression, cytokine profiles, and gene expression, suggesting that these two subsets of NKT cells undergo similar differentiation programs. Hepatic gammadelta NKT cells have an invariant TCR and are derived predominantly from fetal progenitors that expand in the thymus during the first weeks of life. The adult thymus contains these invariant gammadelta NKT cells plus a heterogeneous population of Vgamma1.1(+)Vdelta6.3(+) T cells with diverse CDR3 sequences. This latter population, normally excluded from the liver, escapes the thymus and homes to the liver when Itk is absent. In addition, Itk(-/-) gammadelta NKT cells persistently express high levels of Zbtb16 (PLZF) and Il4, genes that are normally downregulated in the most mature subsets of NKT cells. These data indicate that Itk signaling is required to prevent the expansion of gammadelta NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation.</p>
dc.identifier.submissionpathfaculty_pubs/141
dc.contributor.departmentDepartment of Pathology
dc.source.pages2659-69


This item appears in the following Collection(s)

Show simple item record