With this project we would like to answer the following questions:To what extent do we observe Treg toTh17 conversion in inflammation of the human skin, as elicited in response to general standardized skin injury (i.e. tape-stripping and topical…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint will be the presence of IL-17 producing Tregs in the
tissues obtained from healthy volunteers (after tape-stripping and LTB4
application) and patients with actinic keratosis treated with imiquimod 5%.
Tissues will be analyzed using multicolour immunohistochemistry and
immunofleorescence. We developed a sensitive triple staining that is based on
the detection of CD4 and Foxp3 expression and IL-17 production. Co-localization
of surface differentiation markers, transcription factors and cytokines will be
verified by confocal-microscopy. Tissues will be visualized using microscopy,
photographed and analysed using computer software (Image J).
Secondary outcome
We will use the mentioned in vivo models for human skin inflammation to analyze
the balance of master transcription factors Foxp3 and RORγt through
immunohistochemistry and immunofluorescence. We will study co-localization and
expression of Foxp3, RORγt and IL-17 by confocal microscopy.
Background summary
Psoriasis is a chronic inflammatory skin disease and is caused by a deregulated
immune system. In this project we will focus on different T-cell subsets
contributing to the pathogenesis of psoriasis. More particularly, we will focus
on regulatory T-cells (Tregs) and Thelper-17 cells (Th17). Tregs are important
in the *off-switch* of inflammation, and are characterised by the expression of
CD25 and transcription factor Foxp3. Impaired functioning of these cells is
considered in the context of several auto-immune diseases, such as psoriasis.
In contrast, Th-17 cells are important in the *on-switch* of inflammation, and
are characterised by the expression of transcription factor RORγt and the
production of IL-17. Recent findings demonstrate that under pro-inflammatory
conditions Tregs can differentiate in vitro into inflammation associated
IL-17-producing cells. This conversion is also seen in the peripheral blood
derived-Tregs from severe psoriasis patients. These cells may indeed be
relevant to the local inflammatory processes in the human skin, as we saw
IL-17-producing Foxp3-expressing CD4+ Tcells in lesional skin sections of
psoriasis patients.
Study objective
With this project we would like to answer the following questions:
To what extent do we observe Treg toTh17 conversion in inflammation of the
human skin, as elicited in response to general standardized skin injury (i.e.
tape-stripping and topical LTB4 application)? And what can we learn from the
application of imiquimod 5% (a TLR7/8 ligand and potent immune activator) on
the human skin, concerning Treg and Th17 cells?
Study design
This study is an explorative observational study, in order to assess whether
Treg into Th17 conversion is relevant to the *on switch* for inflammation of
the human skin. We will demonstrate this by using in vivo models for
inflammation, namely tape-stripping, LTB4 and imiquimod 5% application.
Study burden and risks
As twenty participants of our study are healthy volunteers, entering the study
does not lead to direct benefit for them. Before the volunteers will give
informed consent/assent, we will inform them that attending in this research is
not in any way beneficial to the them. When the volunteer, despite of this,
does wish to attend in this study, most likely he/she will do this to make a
contribution to science. Considering this, we are of the opinion that
participation in a study with short follow-up and only minimal invasive
techniques, is legitimate. Tape stripping and LTB4 application has been carried
out by us in the past and has been proven to be painless and without any
discomfort. To obtain the biopsies, participants have to visit the hospital
maximal 6 times. The punch biopsies are taken according to standard procedure
and may be slightly tender. Scar formation does not occur or is barely visible.
Conserning the patients with actinic keratosis, there will be no deviation from
treatment procedures. Patients have to make two extra visits to obtain the
biopsies. The extra visit to obatain the second biopsy can also serve as an
extra control after their treatment with imiquimod 5%. For some patients this
might serve as a small benefit, that comes along with participating in this
study, as normally the first control visit will be 2 months later. The punch
biopsies are taken according to standard procedure and may be slightly tender.
Scar formation does not occur or is barely visible.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers must meet the following criteria:
• Adults older than 18 years of age
• Volunteers must be willing to give a written informed consent
• Volunteers must be able to adhere to the visit schedule;Patients must meet the following criteria:
• Adults older than 18 years of age
• All patients have to have actinic keratosis
• The doctor and the patient decided that the best treatment option is field-treatment with imiquimod 5%
• Patients must be willing to give a written informed consent
• Patients must be able to adhere to the visit schedule
Exclusion criteria
Volunteers will be excluded from this study when any of the following criteria listed below are met:
• Children or adolescents younger than 18 years of age
• Volunteers with a history or signs of psoriasis
• Volunteers with a history or signs of other inflammatory skin diseases, for example atopic dermatitis
• Volunteers exposed to large amounts of sunlight or UV-radiation in the last week
• Volunteers using immunosuppressive agents like prednisone or methotrexate
• Volunteers with relevant co-morbidities
• Volunteers with a current condition involving an activated immune system, such as the flue or a recent vaccination;Patients will be excluded from this study when any of the following criteria listed below are met:
• Children or adolescents younger than 18 years of age
• Patients with a history or signs of psoriasis
• Patients with a history or signs of other inflammatory skin diseases, for example
atopic dermatitis
• Patients exposed to large amounts of sunlight or UV-radiation in the last week
• Patients using immunosuppressive agents like prednisone or methotrexate
• Patients with relevant co-morbidities
• Patients with a current condition involving an activated immune system, such as the
flue or a recent vaccination
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL36165.091.11 |