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Article: Bcl10/Malt1 signaling is essential for TCR-induced NF-κB activation in thymocytes but dispensable for positive or negative selection

TitleBcl10/Malt1 signaling is essential for TCR-induced NF-κB activation in thymocytes but dispensable for positive or negative selection
Authors
Issue Date2007
Citation
Journal of Immunology, 2007, v. 178, n. 2, p. 953-960 How to Cite?
AbstractDuring T cell development in the thymus, high-affinity/avidity TCR engagement induces negative selection by apoptosis, while lower affinity/avidity TCR interactions lead to positive selection and survival of thymocytes. Yet, the mechanisms that discriminate between positive and negative selection are not fully understood. One major regulator of survival and apoptosis in lymphoid cells is the transcription factor NF-κB. Several reports have indicated key roles for NF-κB in positive and negative selection. In peripheral T cells, TCR ligation activates NF-κB through a selective pathway that involves protein kinase Cθ, Bcl10, and Malt1. While protein kinase Cθ is dispensable for thymic TCR signaling, the molecular roles of Bcl10 and Malt1 in thymocytes have not been investigated. In the present study, we show that both Bcl10 and Malt1 are essential for TCR signaling in thymocytes as a genetic disruption of either molecule blocks TCR-induced NF-κB activation in these cells. To investigate the function of this pathway in thymic selection, we introduced tha Bcl10 or Malt1 mutations into three well-established TCR transgenic mouse models. Surprisingly, using several in vivo or in vitro assays, we were unable to demonstrate a role for TCR-induced NF-κB activation in either positive or negative selection. Thus, while TCR signaling to NF-κB controls the activation of mature T cells, we suggest that this pathway is not involved in the positive or negative selection of thymocytes. Copyright © 2007 by The American Association of Immunologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/293098
ISSN
2023 Impact Factor: 3.6
2023 SCImago Journal Rankings: 1.558
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJost, Philipp J.-
dc.contributor.authorWeiss, Stephanie-
dc.contributor.authorFerch, Uta-
dc.contributor.authorGross, Olaf-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorPeschel, Christian-
dc.contributor.authorRuland, Jürgen-
dc.date.accessioned2020-11-17T14:57:52Z-
dc.date.available2020-11-17T14:57:52Z-
dc.date.issued2007-
dc.identifier.citationJournal of Immunology, 2007, v. 178, n. 2, p. 953-960-
dc.identifier.issn0022-1767-
dc.identifier.urihttp://hdl.handle.net/10722/293098-
dc.description.abstractDuring T cell development in the thymus, high-affinity/avidity TCR engagement induces negative selection by apoptosis, while lower affinity/avidity TCR interactions lead to positive selection and survival of thymocytes. Yet, the mechanisms that discriminate between positive and negative selection are not fully understood. One major regulator of survival and apoptosis in lymphoid cells is the transcription factor NF-κB. Several reports have indicated key roles for NF-κB in positive and negative selection. In peripheral T cells, TCR ligation activates NF-κB through a selective pathway that involves protein kinase Cθ, Bcl10, and Malt1. While protein kinase Cθ is dispensable for thymic TCR signaling, the molecular roles of Bcl10 and Malt1 in thymocytes have not been investigated. In the present study, we show that both Bcl10 and Malt1 are essential for TCR signaling in thymocytes as a genetic disruption of either molecule blocks TCR-induced NF-κB activation in these cells. To investigate the function of this pathway in thymic selection, we introduced tha Bcl10 or Malt1 mutations into three well-established TCR transgenic mouse models. Surprisingly, using several in vivo or in vitro assays, we were unable to demonstrate a role for TCR-induced NF-κB activation in either positive or negative selection. Thus, while TCR signaling to NF-κB controls the activation of mature T cells, we suggest that this pathway is not involved in the positive or negative selection of thymocytes. Copyright © 2007 by The American Association of Immunologists, Inc.-
dc.languageeng-
dc.relation.ispartofJournal of Immunology-
dc.titleBcl10/Malt1 signaling is essential for TCR-induced NF-κB activation in thymocytes but dispensable for positive or negative selection-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4049/jimmunol.178.2.953-
dc.identifier.pmid17202357-
dc.identifier.scopuseid_2-s2.0-33846235157-
dc.identifier.volume178-
dc.identifier.issue2-
dc.identifier.spage953-
dc.identifier.epage960-
dc.identifier.isiWOS:000243320400036-
dc.identifier.issnl0022-1767-

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