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Cell Commun Signal ; 22(1): 284, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783329

RESUMO

BACKGROUND: To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs. METHODS: The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting. RESULTS: The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR. CONCLUSIONS: Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR.


Assuntos
Células Dendríticas , Tolerância Imunológica , Interleucina-10 , Telomerase , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Estresse do Retículo Endoplasmático , Interleucina-10/metabolismo , Interleucina-10/genética , Camundongos Endogâmicos BALB C , Rinite Alérgica/imunologia , Telomerase/metabolismo , Telomerase/genética
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