Affiliation:
1. Centre for Dermatology Research University of Manchester & NIHR Biomedical Research Centre Manchester UK
2. Department of Dermatology, Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Salford UK
3. Unilever R&D Colworth Sharnbrook UK
4. Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery University of Miami Coral Gables Florida USA
5. Monasterium Laboratory Münster Germany
6. CUTANEON Hamburg Germany
Abstract
AbstractObjectiveDandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff‐affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune privilege (HF IP) remain unknown. Here, we characterised the HF immune microenvironment and immune privilege status in dandruff‐affected scalp skin.MethodsWe assessed relevant key parameters in healthy versus dandruff‐affected human scalp biopsies using quantitative immunohistomorphometry, laser capture microdissection, and RNA sequencing.ResultsThe number of epidermal CD4+ and CD8+ T cells was increased in lesional dandruff scalp skin, while the number of MHC class II+/CD1a+ Langerhans cells was decreased in the infundibulum. The number of intrafollicular and perifollicular CD4+ T cells and CD8+ T cells, perifollicular CD68+ macrophages, and tryptase+ mast cells remained unchanged. Interestingly, MHC class Ia and ß2‐microglobulin protein expression were significantly increased specifically in the suprabulbar outer root sheath (ORS) compartment of dandruff‐associated HFs. RNAseq analysis of laser capture micro‐dissected suprabulbar ORS compartment revealed antigen presentation pathway as the top regulated canonical pathway, along with the upregulation of HF‐IP genes such as HLA‐C, HLA‐DP, and TAP1, which are normally down‐regulated in healthy HFs. Intrafollicular protein expression of known HF IP guardians (CD200 and α‐MSH) and ‘danger signals’ (MICA and CXCL10) remained unaltered at the IP sites of dandruff lesional HFs compared to non‐lesional and healthy HFs. Instead, the expression of macrophage migration inhibiting factor (MIF), another HF IP guardian, was reduced.ConclusionTogether, this work shows that dandruff is associated with epidermal T‐cell infiltration and a weakened HF IP in the suprabulbar ORS of HFs in dandruff lesional scalp.
Funder
Unilever
Biotechnology and Biological Sciences Research Council
University of Miami