Research

The charity supports the dissemination of research findings, the development of new therapies and the education of future researchers. Dermatrust directly funds one Clinical Research Fellow and one research scientist, both registered for PhD’s, and one Post Doctoral Scientist. Research funded by Dermatrust has been presented at national and international meetings and published in highly respected peer reviewed journals. (see below).

It also contributes to the psycho- dermatology service within The Department of Dermatology at the Royal Free Hospital. This provides much needed help and support with the psychological aspects of skin diseases.
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Research Project investigating the Immune Response in Ageing

Ageing individuals exhibit impaired immune function within the skin manifested by their greater susceptibility to skin infections (such as shingles, caused by reactivation of the varicella zoster virus or VZV), skin cancer, and autoimmune skin diseases. This impairment is also evident from their diminished delayed-type hypersensitivity (DTH) responses to intradermal challenge with a range of recall antigens, including VZV skin test antigen. Vaccination of the elderly is a crucial public health strategy to stimulate immune responses and diminish the impact of infectious diseases in this age group. Zostavax® is a live attenuated shingles vaccine, subcutaneously administered, which is now routinely recommended for the 70-80 age bracket in the UK. This vaccine is known to stimulate VZV-specific CD4+ T cell immunity in the blood, but its mechanism of action on the cutaneous immune system is not fully understood. The current research programme is centred on investigating the extent to which Zostavax boosts skin immunity to VZV and the mechanisms involved.
Healthy volunteers aged over 70 will be recruited into the study and have VZV skin testing and then skin biopsies will be taken from these test sites before and after receiving the shingles vaccine. In a small pilot study the vaccine led to a significant boost in the clinical responses to VZV skin challenge, demonstrating enhanced immune memory in the skin. However in a minority of volunteers there was no improvement, highlighting the ineffectiveness of vaccination in some ageing individuals. These findings were consistent with previous studies investigating the effect of other vaccines on DTH responses in the skin of the elderly. The effect of the vaccine on the kinetics of the DTH response to VZV will be investigated by immunofluorescence microscopy analysis of the numbers and proliferation (Ki67+) of CD4+ and CD8+ effector T cells and CD4+ Foxp3+ regulatory T cells at the test site at Days 3 and 7 after VZV skin challenge. This work will determine whether CD4+ T cells that are required to mount the response are inhibited by the regulatory phenotype (Foxp3+) cells in those that fail to mount a response and on the other hand a reduced inhibitory signalling as a consequence of fewer regulatory T cells at the site of VZV antigen challenge may be a possible mechanism for the vaccine-induced enhancement in the VZV-specific immune response in the skin.
Ageing is characterised by low-level, chronic inflammation, which is associated with adverse health outcomes. Transcriptional analysis of secondary immune responses in the skin has suggested higher levels of non-specific inflammation in older individuals, which may have a role in the impairment of antigen-specific immune responses in this age group. These findings are complemented by analysis of immune signalling defects in T cells of older individuals implicating over-activity of the p38 mitogen activated protein kinase (MAPK) pathway, which has a central role in the biosynthesis of pro-inflammatory cytokines. Consequently, p38 inhibitors have recently been trialled in the treatment of inflammatory diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease. We plan to investigate whether blocking non-specific inflammation via p38 inhibition can boost the DTH response to VZV skin challenge in ageing individuals. The clinical and cellular components of the DTH response will be investigated before and after receiving a 4-day course of losmapimod, an oral p38 MAPK inhibitor. Enhancement of the DTH response following p38 MAPK inhibition may suggest that such pharmacological inhibition may be a useful strategy to boost vaccine responses in the older population.

In order to undertake this 3 year period of research, funding is required for a Post-doctoral scientist costing approximately £168,984 and for a Research Nurse costing £ 143,043.