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Syk inhibition limits autoimmunity and abnormal B cell phenotype and function in mice with B cell-specific TRAF3 deficiency.

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Journal of immunology (Baltimore, Md. : 1950) 📖 저널 OA 60% 2022: 1/2 OA 2025: 5/12 OA 2026: 12/15 OA 2022~2026 2026 Vol.215(4) OA NF-κB Signaling Pathways
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PubMed DOI PMC OpenAlex 마지막 보강 2026-04-30
OpenAlex 토픽 · NF-κB Signaling Pathways Melanoma and MAPK Pathways Protein Tyrosine Phosphatases

Hornick EL, Oxley K, Debreceni IL, Wieting N, Ybarra TK, Hostager BS

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Autoimmune disorders reduce quality of life and lifespan and can increase B cell lymphoma risk.

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APA Emma L Hornick, Kyp Oxley, et al. (2026). Syk inhibition limits autoimmunity and abnormal B cell phenotype and function in mice with B cell-specific TRAF3 deficiency.. Journal of immunology (Baltimore, Md. : 1950), 215(4). https://doi.org/10.1093/jimmun/vkag049
MLA Emma L Hornick, et al.. "Syk inhibition limits autoimmunity and abnormal B cell phenotype and function in mice with B cell-specific TRAF3 deficiency.." Journal of immunology (Baltimore, Md. : 1950), vol. 215, no. 4, 2026.
PMID 42026764 ↗

Abstract

Autoimmune disorders reduce quality of life and lifespan and can increase B cell lymphoma risk. The adaptor protein TRAF3 regulates B cell survival, activation, and differentiation by restraining signaling through Toll-like receptors, tumor necrosis factor (TNF) receptor superfamily members, and the B cell antigen receptor-pathways linked to autoimmunity and lymphoma. Mice lacking TRAF3 in B cells (B-Traf3-/-) develop both autoimmunity and B cell malignancies. TRAF3 negatively regulates activation of spleen tyrosine kinase (Syk), which is involved in multiple B cell signaling pathways. B-Traf3-/- mice treated with the Food and Drug Administration (FDA)-approved Syk inhibitor Fostamatinib, exhibited reduction in autoantibodies, gland inflammation, and expansion of autoimmune-associated B cell populations. Fostamatinib also corrected enhanced pro-survival proteins and aberrant B cell survival in Traf3-/- B cells, without inhibiting humoral responses to immunization. These findings identify elevated Syk activation as a key driver of B cell dysfunction and autoimmunity in B-Traf3-/- mice, suggesting therapeutic potential for Syk inhibitors in conditions linked to decreased B cell TRAF3 levels.

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