Notch signaling in human skin diseases
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Project: Notch signaling in human skin diseases
Lead: Dr Carrie Ambler
In humans, hair follicle clumping or “tufting” occurs in a skin inflammatory disease called tufted hair folliculitis. Tufted hair folliculitis is most often classified as a sub-category of the human cutaneous inflammatory condition keratosis folliculitis decalvans. Clinical studies strongly suggest that human tufted hair folliculitis is caused by a chronic Staphylococcus Aureus infection. Histological data show dermal infiltration of neutrophils and lymphocytes localised adjacent to the upper portion of the hair follicle, and it has been hypothesised that following immunocyte infiltration, fibrosis around the upper follicle results in contraction causing the tufted appearance. Tufted hair folliculitis is also classified as a scarring alopecia, or permanent loss of hair, but a recent study suggests initial tufting arises from hair follicle re-spacing as the lower portion of the hair follicles are retained.
In our studies we found that forced Notch activity in epidermal progenitor cells led to abnormal clumping of hair follicles with the areas in between largely devoid of hair giving the skin a “tufted” appearance. Occasionally, we found hair follicles shared a common infundibulum or upper portion of the follicle, yet the hair follicle bulge and bulb remained distinct. Hair follicle tufting was irreversible as mice retained their tufted phenotype following a 4-month chase period after drug-induced epidermal Notch activity. We have correlative evidence that Notch-induced hair tufting is linked to inflammation. A great number of dermal lymphocytes were found in transgenic mice with evident hair “tufting”. Additionally, injecting mice with the anti-inflammatory dexamethasone while activating the Notch pathway reduced the number of hair tufts. As far as we can discern from the published literature, hair follicle re-spacing leading to “tufting” is unique to our mouse model of skin inflammation.
One goal is to determine whether Notch-induced hair tufting in mice mimics this human inflammatory disease. In collaboration with Dr. Andrew Messenger, a consultant dermatologist at the Royal Hallamshire Hospital in Sheffield, we hope to look at whether samples from human patients with tufted hair folliculitis have evidence of dysregulated Notch signaling.
