Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

2011 ◽  
Vol 52 (7) ◽  
pp. 4447 ◽  
Author(s):  
Michael Kinori ◽  
Jennifer E. Kloepper ◽  
Ralf Paus
2000 ◽  
Vol 142 (5) ◽  
pp. 862-873 ◽  
Author(s):  
T. Christoph ◽  
S. Müller-Röver ◽  
H. Audring ◽  
D.J. Tobin ◽  
B. Hermes ◽  
...  

2020 ◽  
Vol 21 (14) ◽  
pp. 5137
Author(s):  
Jung Eun Kim ◽  
Yu Jin Lee ◽  
Hye Ree Park ◽  
Dong Geon Lee ◽  
Kwan Ho Jeong ◽  
...  

Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/β-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/β-catenin signaling pathway, including Lef1 and β-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of caspase-1, IL-1β, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/β-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege.


Author(s):  
Ralf Paus ◽  
Natsuho Ito ◽  
Masahiro Takigawa ◽  
Taisuke Ito

2014 ◽  
Vol 6 (3) ◽  
pp. 263-266
Author(s):  
Simona Corina ȘENILĂ ◽  
Ovidiu BĂLĂCESCU ◽  
Loredana BĂLĂCESCU ◽  
Elisabeta CANDREA ◽  
Loredana UNGUREANU ◽  
...  

Alopecia areata (AA) is a chronic, T-cell mediated autoimmune disease directed against the hair follicle, which partially evolves due to a loss of the immune privilege of the anagen hair follicle. The immune privilege is maintained by several factors, including a downregulation of MHC class I and II, local immunosupressants and expression of Fas ligand. The purpose of the study was to evaluate several factors involved in the collapse and restoration of the immune privilege. We investigated IDO1, IGF1 and red/IK gene expression in lesional and perilesionalscalp biopsies from alopecia areata patients. Seven paired punch-biopsies were taken from the active edge of alopecic plaque and from the perilesional scalp. Expression of IDO1, IGF1 and red/IK genes was performed by qRT-PCR. In lesional tissue, IGF1, IDO1 and red/IK genes showed an increase in the mRNA levels as compared with the perilesional scalp. By comparing the pairs of data for the investigated genes, IDO1was statistically upregulated in the lesional area. No significant differences were observed between the gene expression in mild or severe AA, from the lesional or perilesional areas. IDO1 mRNA expression was higher in patients with a relapse duration of less than 6 months as compared to patients with a relapse duration of more than 6 months; levels of IGF1 and red/IK mRNA are increased in lesionals compared to perilesional scalp area.


2009 ◽  
Vol 35 (6) ◽  
pp. 637-644 ◽  
Author(s):  
M. J. Harries ◽  
K. C. Meyer ◽  
I. H. Chaudhry ◽  
C. E. M. Griffiths ◽  
R. Paus

2008 ◽  
Vol 128 (5) ◽  
pp. 1196-1206 ◽  
Author(s):  
Taisuke Ito ◽  
Natsuho Ito ◽  
Matthias Saatoff ◽  
Hideo Hashizume ◽  
Hidekazu Fukamizu ◽  
...  

2014 ◽  
Vol 134 (3) ◽  
pp. 736-745 ◽  
Author(s):  
Xiaojie Wang ◽  
Alexandra K. Marr ◽  
Trisia Breitkopf ◽  
Gigi Leung ◽  
Jianqiang Hao ◽  
...  

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