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CD5 dynamically calibrates basal NF-κB signaling in T cells during thymic development and peripheral activation.
Matson, Courtney A; Choi, Seeyoung; Livak, Ferenc; Zhao, Bin; Mitra, Apratim; Love, Paul E; Singh, Nevil J.
Afiliação
  • Matson CA; Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.
  • Choi S; Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
  • Livak F; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
  • Zhao B; Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
  • Mitra A; Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
  • Love PE; Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
  • Singh NJ; Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; nsingh@som.umaryland.edu.
Proc Natl Acad Sci U S A ; 117(25): 14342-14353, 2020 06 23.
Article em En | MEDLINE | ID: mdl-32513716
Immature T cells undergo a process of positive selection in the thymus when their new T cell receptor (TCR) engages and signals in response to self-peptides. As the T cell matures, a slew of negative regulatory molecules, including the inhibitory surface glycoprotein CD5, are up-regulated in proportion to the strength of the self-peptide signal. Together these regulators dampen TCR-proximal signaling and help avoid any subsequent peripheral activation of T cells by self-peptides. Paradoxically, antigen-specific T cells initially expressing more CD5 (CD5hi) have been found to better persist as effector/memory cells after a peripheral challenge. The molecular mechanisms underlying such a duality in CD5 function is not clear. We found that CD5 alters the basal activity of the NF-κB signaling in resting peripheral T cells. When CD5 was conditionally ablated, T cells were unable to maintain higher expression of the cytoplasmic NF-κB inhibitor IκBα. Consistent with this, resting CD5hi T cells expressed more of the NF-κB p65 protein than CD5lo cells, without significant increases in transcript levels, in the absence of TCR signals. This posttranslationally stabilized cellular NF-κB depot potentially confers a survival advantage to CD5hi T cells over CD5lo ones. Taken together, these data suggest a two-step model whereby the strength of self-peptide-induced TCR signal lead to the up-regulation of CD5, which subsequently maintains a proportional reserve of NF-κB in peripheral T cells poised for responding to agonistic antigen-driven T cell activation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Regulação da Expressão Gênica no Desenvolvimento / Antígenos CD5 / Proteína Tirosina Fosfatase não Receptora Tipo 6 / Inibidor de NF-kappaB alfa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Regulação da Expressão Gênica no Desenvolvimento / Antígenos CD5 / Proteína Tirosina Fosfatase não Receptora Tipo 6 / Inibidor de NF-kappaB alfa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article