TLR9-dependent dendritic cell maturation promotes IL-6-mediated upregulation of cathepsin X.
IL‐6
Toll‐like receptors
cathepsin X
dendritic cells
protease regulation
Journal
Immunology and cell biology
ISSN: 1440-1711
Titre abrégé: Immunol Cell Biol
Pays: United States
ID NLM: 8706300
Informations de publication
Date de publication:
09 Jul 2024
09 Jul 2024
Historique:
revised:
23
06
2024
revised:
25
06
2024
received:
19
03
2024
accepted:
26
06
2024
medline:
9
7
2024
pubmed:
9
7
2024
entrez:
9
7
2024
Statut:
aheadofprint
Résumé
Cysteine cathepsins are lysosomal proteases subject to dynamic regulation within antigen-presenting cells during the immune response and associated diseases. To investigate the regulation of cathepsin X, a carboxy-mono-exopeptidase, during maturation of dendritic cells (DCs), we exposed immortalized mouse DCs to various Toll-like receptor agonists. Using a cathepsin X-selective activity-based probe, sCy5-Nle-SY, we observed a significant increase in cathepsin X activation upon TLR-9 agonism with CpG, and to a lesser extent with Pam3 (TLR1/2), FSL-1 (TLR2/6) and LPS (TLR4). Despite clear maturation of DCs in response to Poly I:C (TLR3), cathepsin X activity was only slightly increased by this agonist, suggesting differential regulation of cathepsin X downstream of TLR activation. We demonstrated that cathepsin X was upregulated at the transcriptional level in response to CpG. This occurred at late time points and was not dampened by NF-κB inhibition. Factors secreted from CpG-treated cells were able to provoke cathepsin X upregulation when applied to naïve cells. Among these factors was IL-6, which on its own was sufficient to induce transcriptional upregulation and activation of cathepsin X. IL-6 is highly secreted by DCs in response to CpG but much less so in response to poly I:C, and inhibition of the IL-6 receptor subunit glycoprotein 130 prevented CpG-mediated cathepsin X upregulation. Collectively, these results demonstrate that cathepsin X is differentially transcribed during DC maturation in response to diverse stimuli, and that secreted IL-6 is critical for its dynamic regulation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Miegunyah Fund
Organisme : National Health and Medical Research Council
ID : GNT2011119
Organisme : Australian Research Council
ID : DE180100418
Informations de copyright
© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.
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