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Toll-like Receptor Homologue CD180 Ligation of B Cells Upregulates Type I IFN Signature in Diffuse Cutaneous Systemic Sclerosis.
Erdo-Bonyár, Szabina; Rapp, Judit; Subicz, Rovéna; Filipánits, Kristóf; Minier, Tünde; Kumánovics, Gábor; Czirják, László; Berki, Tímea; Simon, Diána.
Afiliación
  • Erdo-Bonyár S; Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, H-7624 Pécs, Hungary.
  • Rapp J; Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, H-7624 Pécs, Hungary.
  • Subicz R; Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, H-7624 Pécs, Hungary.
  • Filipánits K; Department of Rheumatology and Immunology, Clinical Center, Medical School, University of Pécs, H-7632 Pécs, Hungary.
  • Minier T; Department of Rheumatology and Immunology, Clinical Center, Medical School, University of Pécs, H-7632 Pécs, Hungary.
  • Kumánovics G; Department of Rheumatology and Immunology, Clinical Center, Medical School, University of Pécs, H-7632 Pécs, Hungary.
  • Czirják L; Department of Rheumatology and Immunology, Clinical Center, Medical School, University of Pécs, H-7632 Pécs, Hungary.
  • Berki T; Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, H-7624 Pécs, Hungary.
  • Simon D; Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, H-7624 Pécs, Hungary.
Int J Mol Sci ; 25(14)2024 Jul 20.
Article en En | MEDLINE | ID: mdl-39063175
ABSTRACT
Type I interferon (IFN-I) signaling has been shown to be upregulated in systemic sclerosis (SSc). Dysregulated B-cell functions, including antigen presentation, as well as antibody and cytokine production, all of which may be affected by IFN-I signaling, play an important role in the pathogenesis of the disease. We investigated the IFN-I signature in 71 patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and 33 healthy controls (HCs). Activation via Toll-like receptors (TLRs) can influence the IFN-I signaling cascade; thus, we analyzed the effects of the TLR homologue CD180 ligation on the IFN-I signature in B cells. CD180 stimulation augmented the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in dcSSc B cells (p = 0.0123). The expression of IFN-I receptor (IFNAR1) in non-switched memory B cells producing natural autoantibodies was elevated in dcSSc (p = 0.0109), which was enhanced following anti-CD180 antibody treatment (p = 0.0125). Autoantibodies to IFN-Is (IFN-alpha and omega) correlated (dcSSc p = 0.0003, HC p = 0.0192) and were present at similar levels in B cells from dcSSc and HC, suggesting their regulatory role as natural autoantibodies. It can be concluded that factors other than IFN-alpha may contribute to the elevated IFN-I signature of dcSSc B cells, and one possible candidate is B-cell activation via CD180.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Linfocitos B / Interferón Tipo I / Antígenos CD Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Linfocitos B / Interferón Tipo I / Antígenos CD Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza