资源类型:
期刊
文章类型:
论著
机构:
[1]Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
[2]Division of Dermatology and Venereology, University Hospitals of Geneva, Geneva, Switzerland.
ISSN:
0906-6705
关键词:
dendritic cells
IL-23
Janus kinase inhibitor
macrophages
tofacitinib
摘要:
Several cytokines signalling via Janus Kinase (JAK) proteins have been implicated in the pathogenesis of immune-mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). Tofacitinib, a small JAK inhibitor, is approved for the treatment of RA and has demonstrated good efficacy in psoriasis phase III clinical trials. In this work, we analysed the in vitro effects of tofacitinib on the functions of human dendritic cells (DCs) and macrophages. When assessing the effects of tofacitinib on monocyte-derived DCs, we observed reduced differentiation of monocytes into immature DCs, as evidenced by a decreased transcription of CD209 and CD80. Phenotype assessment in the presence of tofacitinib suggested a switch towards a M1-like macrophage phenotype, as evidenced by the expression of M1 markers such as iNOS, as well as cytokines typically expressed by M1 cells, including IL-12 and IL-23. Of note, Arginase1 and CD200R, typically expressed by M2 cells, were absent on tofacitinib-treated DCs. Furthermore, tofacitinib affected the response of differentiated DCs to maturation stimuli such as LPS and IFNγ, resulting in a partial up-regulation of IL-23 and down-regulation of IL-12, as assessed by qPCR. When investigating macrophage development, we found that tofacitinib inhibited the ability of monocytes to differentiate and polarize into regulatory M2 macrophages, while rather enhancing the ability to develop into inflammatory M1-like macrophages, as evidenced by decreased expression of the M2 marker CD200R and enhanced production of IL-12 and IL-23. In conclusion, tofacitinib impacts the differentiation of human DCs and macrophages, it particularly favours generation of M1-like pro-inflammatory macrophages.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
基金:
The study was partially supported by a grant from Pfizer. Bin Zhang received a Swiss Government Excellence Scholarship.
PubmedID:
31721311
中科院(CAS)分区:
出版当年[2018]版:
大类
|
3 区
医学
小类
|
3 区
皮肤病学
最新[2023]版:
大类
|
3 区
医学
小类
|
3 区
皮肤病学
第一作者:
Stalder Romaine
第一作者机构:
[1]Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
推荐引用方式(GB/T 7714):
Stalder Romaine,Zhang Bin,Jean Wrobel Ludovic,et al.The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development.[J].EXPERIMENTAL DERMATOLOGY.2019,doi:10.1111/exd.14059.
APA:
Stalder Romaine,Zhang Bin,Jean Wrobel Ludovic,Boehncke Wolf-Henning&Brembilla Nicolo Costantino.(2019).The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development..EXPERIMENTAL DERMATOLOGY,,
MLA:
Stalder Romaine,et al."The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development.".EXPERIMENTAL DERMATOLOGY .(2019)