Related resources
Search for item elsewhere
University researcher(s)
Academic department(s)
Immunopathogenesis of Primary Cicatricial Alopecia
[Thesis]. Manchester, UK: The University of Manchester; 2013.
Access to files
-
FULL-TEXT.PDF (pdf)
Abstract
The current thesis project contributes to examining the immunopathogenesis of lichen planopilaris (LPP), one of the most frequent and the best-studied forms of scarring hair loss (primary cicatricial alopecia [PCA]) and an excellent model for the lymphocytic, inflammatory type of PCA. Current LPP pathobiology concepts propose that scarring hair loss in LPP results from an inflammatory attack that is associated with a collapse of the relative immune privilege of the hair follicle (HF), which irreversibly damages the epithelial stem cells in the bulge region of the HF. This is thought to limit the HF’s capacity to cyclically regenerate itself, thus causing permanent hair loss. The current thesis project aimed to establish a basic understanding of human HF anatomy, function, and immunology and to acquire fundamental methodological skills for investigating human hair follicle pathology by employing appropriate histochemical and immunohistological markers. An array of histochemical, immunohistological techniques for examining the inflammatory infiltrates of lesional versus non-lesional HFs in scalp skin biopsies from patients with LPP and HFs from healthy scalp skin was established. This included H&E, mast cell histochemistry (toluidine blue) and immunohistochemistry (tryptase), and immunohistological markers for macrophages (CD163), natural killer (NK) cells (CD161, V alpha 24), regulatory T cells (FOXP3), and EMT markers (E-cadherin, vimentin). Perifollicular mast cells and macrophages were also evaluated. This revealed an increased number of degranulated mast cells in the perifollicular mesenchyme of LPP HFs compared to controls. It could also be shown that the number of resident (CD163+) macrophages in the HF’s connective tissue sheath, unexpectedly, is significantly reduced around LPP HFs compared to controls. Quantitative immunohistomorphometry was employed to gauge whether there are any phenomenological indications that HF epithelial stem cells are undergoing a transition to mesenchymal cells (EMT). The epithelial cell-specific adhesion molecule, E-cadherin, was significantly reduced in the bulge area of lesional LPP HFs, while the mesenchyme-specific marker, vimentin, was up-regulated here. These immunohistomorphometry results were supplemented by quantitative RT-PCR, which showed a trend towards a reduction of E-cadherin and towards an up-regulation of vimentin expression in the bulge region of lesional HFs from LPP patients, though significance was not reached.Taken together, the current thesis project has made an instructive panel of antigens and new immunostaining protocols available for systematic quantitative analysis in future LPP research. Most importantly, the project has generated the first exciting pointers in support of the hypothesis that the extensive scarring in PCAs may indeed result from pathological EMT in the epithelial stem cell zone of the HF, the bulge.
Layman's Abstract
The current thesis project contributes to examining the immunopathogenesis of lichen planopilaris (LPP), one of the most frequent and the best-studied forms of scarring hair loss (primary cicatricial alopecia [PCA]) and an excellent model for the lymphocytic, inflammatory type of PCA. Current LPP pathobiology concepts propose that scarring hair loss in LPP results from an inflammatory attack that is associated with a collapse of the relative immune privilege of the hair follicle (HF), which irreversibly damages the epithelial stem cells in the bulge region of the HF. This is thought to limit the HF’s capacity to cyclically regenerate itself, thus causing permanent hair loss. The current thesis project aimed to establish a basic understanding of human HF anatomy, function, and immunology and to acquire fundamental methodological skills for investigating human hair follicle pathology by employing appropriate histochemical and immunohistological markers. An array of histochemical, immunohistological techniques for examining the inflammatory infiltrates of lesional versus non-lesional HFs in scalp skin biopsies from patients with LPP and HFs from healthy scalp skin was established. This included H&E, mast cell histochemistry (toluidine blue) and immunohistochemistry (tryptase), and immunohistological markers for macrophages (CD163), natural killer (NK) cells (CD161, V alpha 24), regulatory T cells (FOXP3), and EMT markers (E-cadherin, vimentin). Perifollicular mast cells and macrophages were also evaluated. This revealed an increased number of degranulated mast cells in the perifollicular mesenchyme of LPP HFs compared to controls. It could also be shown that the number of resident (CD163+) macrophages in the HF’s connective tissue sheath, unexpectedly, is significantly reduced around LPP HFs compared to controls. Quantitative immunohistomorphometry was employed to gauge whether there are any phenomenological indications that HF epithelial stem cells are undergoing a transition to mesenchymal cells (EMT). The epithelial cell-specific adhesion molecule, E-cadherin, was significantly reduced in the bulge area of lesional LPP HFs, while the mesenchyme-specific marker, vimentin, was up-regulated here. These immunohistomorphometry results were supplemented by quantitative RT-PCR, which showed a trend towards a reduction of E-cadherin and towards an up-regulation of vimentin expression in the bulge region of lesional HFs from LPP patients, though significance was not reached.Taken together, the current thesis project has made an instructive panel of antigens and new immunostaining protocols available for systematic quantitative analysis in future LPP research. Most importantly, the project has generated the first exciting pointers in support of the hypothesis that the extensive scarring in PCAs may indeed result from pathological EMT in the epithelial stem cell zone of the HF, the bulge.