Logo del repository
  1. Home
 
Opzioni

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation

Lougaris, V.
•
Baronio, M.
•
Vitali, M.
altro
Plebani, A.
2014
  • journal article

Periodico
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Abstract
BACKGROUND: Bruton tyrosine kinase (BTK) plays an essential role in various biologic functions of different cell types. Mutations in BTK lead to X-linked agammaglobulinemia (XLA) in humans. BTK was recently linked to the innate immune system, in particular, the Toll-like receptor (TLR) pathway; however, the TLR9 pathway has never been studied in dendritic cells (DCs) of patients with XLA. OBJECTIVE: The aim of this study was to investigate the role of BTK in human DC activation upon TLR9 stimulation. METHODS: DCs of patients with XLA and healthy donors were stimulated via TLR4/9 and evaluated for cell activation and cytokine production. RESULTS: We showed that BTK plays an essential role in DC responses to unmethylated CpG oligodeoxynucleotide: although responses to lipopolysaccaride/TLR4 induce normal DC activation in terms of upregulation of specific markers (CD86, CD83, CD80, HLA-DR), the CpG/TLR9 pathway is completely impaired in patients with XLA. Furthermore, cytokine production upon TLR9 activation in patients with XLA is radically impaired in terms of IL-6, IL-12, TNF-α, and IL-10 production. Interestingly, BTK mediated STAT1/3 upregulation in a TLR9-dependent manner. The important role of BTK in human DC activation was confirmed after incubation of healthy DCs with ibrutinib, the specific BTK inhibitor, which resulted in impairment of TLR9 responses as seen in patients with XLA. CONCLUSION: Analysis of these data suggests that BTK regulates human DC responses upon TLR9 engagement in terms of activation, cytokine production, and STAT1/3 upregulation. These findings may be of important significance for better understanding and managing different clinical conditions, such as agammaglobulinemia and lymphoid malignancies.
DOI
10.1016/j.jaci.2013.12.1085
WOS
WOS:000336672500017
Archivio
http://hdl.handle.net/11368/2843863
info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84901801796
Diritti
closed access
license:digital rights management non definito
FVG url
https://arts.units.it/request-item?handle=11368/2843863
Soggetti
  • BTK, STAT1, STAT3, TL...

Web of Science© citazioni
55
Data di acquisizione
Mar 21, 2024
Visualizzazioni
2
Data di acquisizione
Apr 19, 2024
Vedi dettagli
google-scholar
Get Involved!
  • Source Code
  • Documentation
  • Slack Channel
Make it your own

DSpace-CRIS can be extensively configured to meet your needs. Decide which information need to be collected and available with fine-grained security. Start updating the theme to match your nstitution's web identity.

Need professional help?

The original creators of DSpace-CRIS at 4Science can take your project to the next level, get in touch!

Realizzato con Software DSpace-CRIS - Estensione mantenuta e ottimizzata da 4Science

  • Impostazioni dei cookie
  • Informativa sulla privacy
  • Accordo con l'utente finale
  • Invia il tuo Feedback