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Investigating dysbiosis of hair follicle immune privilege in the pathogenesis of dandruff


Project Description

Dandruff is characterised by excess skin shedding, hyperkeratosis, parakeratosis and immune cell infiltration (1). It is considered a multifactorial condition with both microbial colonisation and host factors such as sebum production thought to play a role. The very visible flakes on the scalp causes a psycho-social burden on an individual. Yet despite this, the mechanisms of dandruff aetiology are poorly understood.

With the onset of dandruff an accompanying inflammatory response can be detected histologically with a substantial increase in immune cell infiltration in the perifollicular dermis1. In this context, is important to note that the hair follicle (HF) is an immune-privileged (IP) mini-organ (2,3). To maintain this immunoinhibitory environment the HF actively suppresses inflammation and promotes immune tolerance by expressing low levels of MHC-class I and “danger” signals like MICA and high levels of immunoinhibitory proteins e.g. alpha-MSH, TGF-beta-1/2 as well as the “no danger” signal, CD200 (2–5). Together these mechanisms are able to prevent immune cell attack and inhibit gamma-delta-T cells, CD8 T cells, macrophages and NK cells e.t.c6.

The loss of any of these mechanisms promotes IP-collapse which we have shown leads to conditions such as alopecia areata. As dandruff occurs exclusively in hair-bearing skin and shows immune infiltration, HF-IP-collapse may be an important factor in dandruff pathogenesis, however, IP status and the perifollicular immune-environment has not been investigated in this scalp condition. Therefore, we hypothesis a dysbiosis in the immune-microenvironment contributes to dandruff pathogenesis.

Entry Requirements
Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in a biological science. A Masters degree in a relevant subject and/or experience in a research setting is desirable.

Funding Notes

BBSRC iCASE Award with Unilever. Studentship funding is for a duration of four years and covers UK/EU tuition fees and an annual minimum stipend of £18777 per annum (2019/20). On the online application form select PhD Dermatological Sciences.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Kerr, K. et al. Epidermal changes associated with symptomatic resolution of dandruff: Biomarkers of scalp health. Int. J. Dermatol. 50, 102–113 (2011).

2. Paus, R., Nickoloff, B. J. & Ito, T. A ‘hairy’ privilege. Trends Immunol. 26, 32–40 (2005).

3. Paus, R., Bulfone-Paus, S. & Bertolini, M. Hair Follicle Immune Privilege Revisited: The Key to Alopecia Areata Management. J. Investig. Dermatology Symp. Proc. 19, S12–S17 (2018).

4. Ito, T. et al. Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. Am. J. Pathol. 164, 623–34 (2004).

5. Meyer, K. C. et al. Evidence that the bulge region is a site of relative immune privilege in human hair follicles. Br. J. Dermatol. 159, 1077–1085 (2008).

6. Ito, T. et al. Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. J. Invest. Dermatol. 128, 1196–206 (2008).

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