ARID5B is a negative modulator of IL-6 production in rheumatoid arthritis synovial fibroblasts.
Immunol Med
; 47(3): 176-185, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38747454
ABSTRACT
Recent single-cell RNA-sequencing analysis of rheumatoid arthritis (RA) synovial tissues revealed the heterogeneity of RA synovial fibroblasts (SFs) with distinct functions such as high IL-6 production. The molecular mechanisms responsible for high IL-6 production will become a promising drug target of RASFs to treat RA. In this study, we performed siRNA screening of 65 transcription factors (TFs) differentially expressed among RASF subsets to identify TFs involved in IL-6 production. The siRNA screening identified 7 TFs including ARID5B, a RA risk gene, that affected IL-6 production. Both long and short isoforms of ARID5B were expressed and negatively regulated by TNF-α in RASFs. The siRNA knockdown and lentiviral overexpression of long and short isoforms of ARID5B revealed that the long isoform suppressed IL-6 production stimulated with TNF-α. eQTL analysis using 58 SFs demonstrated that RA risk allele, rs10821944, in intron 4 of the ARID5B gene had a trend of eQTL effects to the expression of long isoform of ARID5B in SFs treated with TNF-α. ARID5B was found to be a negative modulator of IL-6 production in RASFs. The RA risk allele of ARID5B intron may cause high IL-6 production, suggesting that ARID5B will become a promising drug target to treat RA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Membrana Sinovial
/
Factores de Transcripción
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Interleucina-6
/
Factor de Necrosis Tumoral alfa
/
Proteínas de Unión al ADN
/
Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
Immunol Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón