Toll-like Receptor Homologue CD180 Ligation of B Cells Upregulates Type I IFN Signature in Diffuse Cutaneous Systemic Sclerosis.
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
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Linfocitos B
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Interferón Tipo I
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Antígenos CD
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Mol Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Hungria