Epithelial-to-Mesenchymal Stem Cell Transition in a Human Organ: Lessons from Lichen Planopilaris

Imanishi, Hiroyasu; Ansell, David M.; Chéret, Jérémy; Harries, Matthew; Bertolini, Marta; Sepp, Norbert; Bı́ró, Tamás; Poblet, Enrique; Jiménez, Francisco; Hardman, Jonathan A.; Panicker, Sreejith Parameswara; Ward, Christopher M.; Paus, Ralf

doi:10.1016/j.jid.2017.09.047

Cited by 62 publications

(122 citation statements)

References 35 publications

(67 reference statements)

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“…Inhibition of 7‐DHCR, or addition of exogenous 7‐dehydrocholesterol (7‐DHC) to human primary outer root sheath keratinocytes (ORSK) or via topical application to mouse back skin, resulted in a pro‐inflammatory response, including upregulation of Toll‐like receptor and interferon signalling networks. Inhibition of cholesterol biosynthesis also upregulated transforming growth factor β (TGFβ1), an established inducer of catagen and fibrosis …”

Section: Associations Between Cholesterol and Hair Pathologiesmentioning

confidence: 94%

“…However, other properties of PPARγ activity (ie anti‐inflammatory effects and epithelial to mesenchymal transition inhibition) are also likely play an important role in disease development . Interestingly, the PPARγ agonist pioglitazone is now being successfully used to treat this disorder, with response rates of over 50% reported .…”

Section: Associations Between Cholesterol and Hair Pathologiesmentioning

confidence: 99%

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Cholesterol homeostasis: Links to hair follicle biology and hair disorders

Palmer

Blakeborough

Harries

et al. 2019

Experimental Dermatology

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Lipids and lipid metabolism are critical factors in hair follicle (HF) biology, and cholesterol has long been suspected of influencing hair growth. Altered cholesterol homeostasis is involved in the pathogenesis of primary cicatricial alopecia, mutations in a cholesterol transporter are associated with congenital hypertrichosis, and dyslipidaemia has been linked to androgenic alopecia. The underlying molecular mechanisms by which cholesterol influences pathways involved in proliferation and differentiation within HF cell populations remain largely unknown. As such, expanding our knowledge of the role for cholesterol in regulating these processes is likely to provide new leads in the development of treatments for disorders of hair growth and cycling. This review describes the current state of knowledge with respect to cholesterol homeostasis in the HF along with known and putative links to hair pathologies.

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Section: Associations Between Cholesterol and Hair Pathologiesmentioning

confidence: 94%

Section: Associations Between Cholesterol and Hair Pathologiesmentioning

confidence: 99%

Cholesterol homeostasis: Links to hair follicle biology and hair disorders

Palmer

Blakeborough

Harries

et al. 2019

Experimental Dermatology

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“…Since all PPARs are widely expressed in human skin and its appendages, there is increasing interest in their role in maintaining cutaneous homeostasis and in dermatological disorders . PPAR‐mediated signalling has attracted special interest in psoriasis, atopic dermatitis, acne, skin ageing, scleroderma, melasma, lipodystrophy and skin cancer . In the context of this Focus Theme Issue , this development encourages one to also take a closer look at why and how exactly PPARs are of special interest in a translational hair research context, with a strict focus on their best‐investigated isoform, PPAR‐γ.…”

Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

“…A major development in scarring alopecia research in general, and LPP pathobiology specifically, is the recognition that pathological epithelial‐mesenchymal transition (EMT) of K15 + human bulge HFeSCs occurs in these diseases, explaining why HFs are not only lost, but also why there is significant fibrosis (“scarring”) . During EMT, epithelial cells lose cell‐to‐cell contact and polarity, adopting a mesenchymal phenotype, that translates to progressive replacement of HF epithelium with fibrous tissue . Therefore, agents that can prevent, or even reverse, pathological EMT may be of major clinical benefit in the management of scarring alopecias such as LPP and FFA.…”

Section: The Importance Of Ppar‐γ For the Bulge Stem Cells And Its Rementioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

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“…11,24,39,45 Human anagen HFs maintain their IP, reducing the opportunity for NK cell activation, thereby escaping the induction of autoimmune disorders such as lichen planopilaris. 24,39,40 F I G U R E 3 UVB preirradiation alone achieved long-term survival of HF allografts. 24,39,40 F I G U R E 3 UVB preirradiation alone achieved long-term survival of HF allografts.…”

Section: Discussionmentioning

confidence: 99%

UVB-induced depletion of donor-derived dendritic cells prevents allograft rejection of immune-privileged hair follicles in humanized mice

Kim

Kang

Park

et al. 2019

American Journal of Transplantation

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Dendritic cells (DCs) are key targets for immunity and tolerance induction; they present donor antigens to recipient T cells by donor-and recipient-derived pathways.Donor-derived DCs, which are critical during the acute posttransplant period, can be depleted in graft tissue by forced migration via ultraviolet B light (UVB) irradiation. Here, we investigated the tolerogenic potential of donor-derived DC depletion through in vivo and ex vivo UVB preirradiation (UV) combined with the injection of anti-CD154 antibody (Ab) into recipients in an MHC-mismatched hair follicle (HF) allograft model in humanized mice. Surprisingly, human HF allografts achieved longterm survival with newly growing pigmented hair shafts in both Ab-treated groups (Ab-only and UV plus Ab) and in the UV-only group, whereas the control mice rejected all HF allografts with no hair regrowth. Perifollicular human CD3 + T cell and MHC class II + cell infiltration was significantly diminished in the presence of UV and/ or Ab treatment. HF allografts in the UV-only group showed stable maintenance of the immune privilege in the HF epithelium without evidence of antigen-specific T cell tolerance, which is likely promoted by normal HFs in vivo. This immunomodulatory strategy targeting the donor tissue exhibited novel biological relevance for clinical allogeneic transplantation without generalized immunosuppression. K E Y W O R D S basic (laboratory) research/science, dendritic cell, dermatology, immunosuppression/immune modulation, stem cells, tissue (nonvascularized) transplantation, tolerance, experimental, translational research/science | 1345 KIM et al.

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Epithelial-to-Mesenchymal Stem Cell Transition in a Human Organ: Lessons from Lichen Planopilaris

Cited by 62 publications

References 35 publications

Cholesterol homeostasis: Links to hair follicle biology and hair disorders

Cholesterol homeostasis: Links to hair follicle biology and hair disorders

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

UVB-induced depletion of donor-derived dendritic cells prevents allograft rejection of immune-privileged hair follicles in humanized mice

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