Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

The adaptor protein TASL is required for age-related B cell emergence and lupus-like disease development in mice.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2003]-
    • Subject Terms:
      Lupus Erythematosus, Systemic*/immunology ; Lupus Erythematosus, Systemic*/metabolism ; Lupus Erythematosus, Systemic*/genetics ; Lupus Erythematosus, Systemic*/pathology ; B-Lymphocytes*/immunology ; B-Lymphocytes*/metabolism ; Aging*/immunology ; Adaptor Proteins, Signal Transducing*/genetics ; Adaptor Proteins, Signal Transducing*/metabolism; Toll-Like Receptor 9/metabolism ; Toll-Like Receptor 7/metabolism ; Interferon Regulatory Factors/metabolism ; Animals ; Mice ; Mice, Inbred C57BL ; Disease Models, Animal ; Female ; Mice, Knockout ; Autoimmunity ; Signal Transduction
    • Abstract:
      The autoimmune disease systemic lupus erythematosus (SLE) is associated with genetic variants in the X-linked gene CXORF21, which encodes the protein TASL. TASL acts as an adaptor in the IRF5 pathway and is necessary for the phosphorylation of IRF5 in response to TLR7 or TLR9 stimulation. Here, we investigate the role of TASL in the humoral immune response, and in the development of lupus in the B6.MRLlpr murine model of SLE. We find that while TASL is dispensable for their development, it is required for the full activation of B cells via TLR9 stimulation, and consequent interferon signaling and inflammatory cytokine expression. Additionally, TASL is crucial for the emergence of age-associated B cells (ABCs), a B cell population derived from the extrafollicular response that increases with age and is expanded in autoimmune disease, and the production of IgG2c antibodies. We also find that deletion of TASL prevents the onset of autoimmunity in the genetically-determined B6.MRLlpr model of lupus.
      (Copyright: © 2026 Johnstone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
    • Abstract:
      The authors have declared that no competing interests exist.
    • Accession Number:
      0 (Toll-Like Receptor 9)
      0 (Toll-Like Receptor 7)
      0 (Interferon Regulatory Factors)
      0 (Irf5 protein, mouse)
      0 (Tlr9 protein, mouse)
      0 (Adaptor Proteins, Signal Transducing)
    • Publication Date:
      Date Created: 20260305 Date Completed: 20260312 Latest Revision: 20260312
    • Publication Date:
      20260312
    • Accession Number:
      PMC12974799
    • Accession Number:
      10.1371/journal.pbio.3003342
    • Accession Number:
      41785302