Tofacitinib downregulates antiviral immune defence in keratinocytes and reduces T cell activation.
Antiviral immunity
Janus kinase inhibitor
Keratinocyte
T cell
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
21 05 2021
21 05 2021
Historique:
received:
05
01
2021
accepted:
12
04
2021
entrez:
22
5
2021
pubmed:
23
5
2021
medline:
30
6
2021
Statut:
epublish
Résumé
Tofacitinib is a novel Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. In clinical trials, the most common adverse events observed were nasopharyngitis, upper respiratory tract infections, and zoster. JAKs are found downstream of the type II cytokine receptor family used by a number of T We treated primary human keratinocytes and synoviocytes with tofacitinib and subsequently added various cytokines and bacterial surface proteins before evaluation of the response via RT-qPCR. CD69 expression on tofacitinib-treated PBMCs was investigated via flow cytometry. We found a markedly reduced gene expression of all tested antiviral peptides such as MX1 or ISG15 in keratinocytes and synoviocytes in the presence of tofacitinib in vitro. Additionally, we found that JAK inhibition reduced activation of T cells after stimulation with bacterial LPS or viral VZV gE. The antiviral immunity is strongly inhibited in the presence of tofacitinib in vitro, while the antimicrobial immunity does not seem to be affected. In T cells, the overall activation process seems to be influenced by tofacitinib. These findings suggest that tofacitinib has an impact on antiviral immunity such as patients treated with tofacitinib often show adverse events like herpes zoster.
Sections du résumé
BACKGROUND
Tofacitinib is a novel Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. In clinical trials, the most common adverse events observed were nasopharyngitis, upper respiratory tract infections, and zoster. JAKs are found downstream of the type II cytokine receptor family used by a number of T
METHODS
We treated primary human keratinocytes and synoviocytes with tofacitinib and subsequently added various cytokines and bacterial surface proteins before evaluation of the response via RT-qPCR. CD69 expression on tofacitinib-treated PBMCs was investigated via flow cytometry.
RESULTS
We found a markedly reduced gene expression of all tested antiviral peptides such as MX1 or ISG15 in keratinocytes and synoviocytes in the presence of tofacitinib in vitro. Additionally, we found that JAK inhibition reduced activation of T cells after stimulation with bacterial LPS or viral VZV gE.
CONCLUSIONS
The antiviral immunity is strongly inhibited in the presence of tofacitinib in vitro, while the antimicrobial immunity does not seem to be affected. In T cells, the overall activation process seems to be influenced by tofacitinib. These findings suggest that tofacitinib has an impact on antiviral immunity such as patients treated with tofacitinib often show adverse events like herpes zoster.
Identifiants
pubmed: 34020693
doi: 10.1186/s13075-021-02509-8
pii: 10.1186/s13075-021-02509-8
pmc: PMC8138978
doi:
Substances chimiques
Antiviral Agents
0
Piperidines
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Pyrroles
0
tofacitinib
87LA6FU830
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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