The role of unconventional T cells in skin inflammation
1 Formål
Unconventional T cells are abundant in mucosal barrier sites and the skin. They are known to play a role in several immune mediated diseases, but their role in inflammatory skin disease is poorly characterized. Several inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa (HS), lead to a significant decrease in quality of life due to their chronic nature. For skin disease HS the treatment options are very limited due to the lack of knowledge of the pathogenesis. Pharmaceutical preparation of cream containing 5% of imiquimod (IMQ/“Aldara”) induces IL-17-driven inflammation when applied to naïve murine skin, and is widely used as a mouse model for psoriasis/skin inflammation. We want to utilize this murine model of IL-17 driven inflammation to investigate the role of unconventional T cells in skin inflammation relevant for psoriasis and HS. Further we will use oxazolone (and other similar oxazoles), a known NKT- dependent irritant, to create skin inflammation in mice.
2 Skadevirkninger
We do not expect the animals to experience any discomfort relating to the application of cream, and we expect minimal discomfort relating to small and superficial wounds after skin biopsies.
We do not expect any major impairment of the animals welfare or general condition, but they might have some itch or discomfort after several days of application of IMQ or oxazoles.
3 Forventet nytteverdi
By investigating the role of unconventional T cells in mice we seek to get increased knowledge about the processes involved in skin inflammation, which could possibly lead to the development of new treatment for diseases such as HS.
4 Antall dyr og art
Mus musculus, 900 animals in total.
5 Hvordan etterleve 3R
The replacement option is not applicable since our hypothesis needs to be tested in a complete animal. Experiments without animals are also planned, but these will be complementary.
The n-value is 9 in each group, the lowest possible number to ensure trustworthy repeatability.
Collaborators have broad experience with this method and the method is well established (see attachment, van der Fits et al., 2009)). Applicant has experience with similar experiments with other irritant. Pain relief is included.
Unconventional T cells are abundant in mucosal barrier sites and the skin. They are known to play a role in several immune mediated diseases, but their role in inflammatory skin disease is poorly characterized. Several inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa (HS), lead to a significant decrease in quality of life due to their chronic nature. For skin disease HS the treatment options are very limited due to the lack of knowledge of the pathogenesis. Pharmaceutical preparation of cream containing 5% of imiquimod (IMQ/“Aldara”) induces IL-17-driven inflammation when applied to naïve murine skin, and is widely used as a mouse model for psoriasis/skin inflammation. We want to utilize this murine model of IL-17 driven inflammation to investigate the role of unconventional T cells in skin inflammation relevant for psoriasis and HS. Further we will use oxazolone (and other similar oxazoles), a known NKT- dependent irritant, to create skin inflammation in mice.
2 Skadevirkninger
We do not expect the animals to experience any discomfort relating to the application of cream, and we expect minimal discomfort relating to small and superficial wounds after skin biopsies.
We do not expect any major impairment of the animals welfare or general condition, but they might have some itch or discomfort after several days of application of IMQ or oxazoles.
3 Forventet nytteverdi
By investigating the role of unconventional T cells in mice we seek to get increased knowledge about the processes involved in skin inflammation, which could possibly lead to the development of new treatment for diseases such as HS.
4 Antall dyr og art
Mus musculus, 900 animals in total.
5 Hvordan etterleve 3R
The replacement option is not applicable since our hypothesis needs to be tested in a complete animal. Experiments without animals are also planned, but these will be complementary.
The n-value is 9 in each group, the lowest possible number to ensure trustworthy repeatability.
Collaborators have broad experience with this method and the method is well established (see attachment, van der Fits et al., 2009)). Applicant has experience with similar experiments with other irritant. Pain relief is included.