Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: Bethesda, MD : American Association of Immunologists
      Original Publication: Baltimore : Williams & Wilkins, c1950-
    • Subject Terms:
      Hematopoiesis/*immunology ; Hepatocyte Nuclear Factor 1-alpha/*physiology ; T-Lymphocytes, Regulatory/*immunology ; Thymus Gland/*immunology; Animals ; Cell Lineage/immunology ; Cell Proliferation ; Forkhead Transcription Factors/metabolism ; Gene Expression Profiling ; Hematopoiesis/genetics ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Proteome/analysis ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/cytology ; beta Catenin/metabolism
    • Abstract:
      Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we identified TCF7 as a promising candidate. Genetic elimination of transcription factor 7 (TCF7) led to increased fractions of Tregs in the thymus. Reduced levels of TCF7, found in the heterozygote, resulted in a greater potential for Treg precursors to differentiate into the Treg lineage. In contrast, activation of TCF7 through β-catenin had the opposite effect. TCF7 levels influenced the required TCR signaling strength of Treg precursors, and TCF7 deficiency broadened the repertoire and allowed lower TCR affinities to be recruited into the Treg lineage. FOXP3 was able to repress TCF7 protein expression. In summary, we propose a regulatory role for TCF7 in limiting access to the Treg lineage.
      (Copyright © 2015 by The American Association of Immunologists, Inc.)
    • Accession Number:
      0 (Forkhead Transcription Factors)
      0 (Foxp3 protein, mouse)
      0 (Hepatocyte Nuclear Factor 1-alpha)
      0 (Hnf1a protein, mouse)
      0 (Proteome)
      0 (beta Catenin)
    • Publication Date:
      Date Created: 20150902 Date Completed: 20160202 Latest Revision: 20150919
    • Publication Date:
      20240829
    • Accession Number:
      10.4049/jimmunol.1500821
    • Accession Number:
      26324778