A Biologist'S Reflections on Dermatology

Billingham, R. E.; Silvers, Willys K.

doi:10.1111/1523-1747.ep12261543

Cited by 69 publications

(51 citation statements)

References 35 publications

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“…The expression of MHCI and MHCII molecules (and other immune system genes) are downregulated in normal human anagen (growing) hair follicles, and because of this, portions of the hair follicle are considered an anatomic compartment with immune privilege (IP; refs. [36][37][38][39]. In the setting of autoimmune or inflammatory diseases associated with hair loss, there is felt to be a loss of IP as evidenced by increases in the expression of MHCI and MHCII molecules as well as other immunoregulatory proteins (40).…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

Pollack

Sapkota

Cartee

2011

Clinical Cancer Research

142

114

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Purpose: Diverse immune-related effects occur with the use of epidermal growth factor receptor inhibitors (EGFRI). In addition to the cutaneous inflammation induced by EGFRIs, these agents have been associated with the exacerbation of autoimmune skin disease and contact hypersensitivity, antiviral effects, and fatal alveolar damage in the setting of lung transplantation. Because EGFR ligands can modulate MHC class I (MHCI) and II (MHCII) molecule expression, we hypothesized that some of the immune-related effects of EGFRIs are due to direct effects on the expression of MHCI and/or MHCII molecules.Experimental Design: Primary human keratinocytes and a malignant keratinocyte cell line (A431) were treated with EGFRIs alone or prior to IFN-g, a potent inducer of MHCI and MHCII molecule expression. CIITA, MHCI, and MHCII RNA expression was measured using quantitative real-time reverse transcriptase PCR, and cell surface MHCI and MHCII protein expression was measured using flow cytometry. Skin biopsies from patients were analyzed for MHCI and MHCII protein expression before and during therapy with an EGFRI using immunohistochemistry.Results: Both EGFR tyrosine kinase inhibitors and ligand-blocking antibodies (cetuximab) augmented the induction of MHCI and MHCII molecules by IFN-g in primary and malignant human keratinocytes. Unexpectedly, the increase in MHCI protein expression did not require the presence of IFN-g. Consistent with these in vitro findings, skin biopsies from cancer patients exhibited increased epidermal MHCI protein expression during therapy with an EGFRI as well as increases in MHCI and MHCII molecule RNA.Conclusions: These studies suggest that EGFRIs may influence immune/inflammatory responses by directly modulating MHC expression. Clin Cancer Res; 17(13); 4400-13. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

Pollack

Sapkota

Cartee

2011

Clinical Cancer Research

142

114

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“…Long before any of this had been known, Billingham proposed that the anagen hair follicle represents a site of immune privilege (63). This resulted from his observation that transplanted allogeneic epidermal melanocytes can escape rejection by the host's immune system by seeking residence in the proximal anagen hair bulb.…”

Section: Immune Privilege Collapsementioning

confidence: 99%

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Gilhar¹,

Paus²,

Kalish³

2007

J. Clin. Invest.

272

278

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Many lessons in autoimmunity -particularly relating to the role of immune privilege and the interplay between genetics and neuroimmunology -can be learned from the study of alopecia areata, the most common cause of inflammation-induced hair loss. Alopecia areata is now understood to represent an organ-restricted, T cell-mediated autoimmune disease of hair follicles. Disease induction is associated with collapse of hair follicle immune privilege in both humans and in animal models. Here, the role of HLA associations, other immunogenetic factors, and neuroendocrine parameters in alopecia areata pathogenesis are reviewed. This instructive and clinically significant model disease deserves more widespread interest in the immunology community.Nonstandard abbreviations used: AA, alopecia areata; AIRE, autoimmune regulator; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; IP-10, IFN-g-inducible protein 10; MIC, MHC class I chain-related; MIF, macrophage migration inhibitory factor; α-MSH, α-melanocyte-stimulating hormone; NALP1, NACHT leucine-rich-repeat protein 1; NGF, nerve growth factor.

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“…Though this important study showed the feasibility of human follicle growth in vitro, the observations obtained with this culture system may not fully reflect follicular growth characteristics in vivo, since individual, mechanically isolated follicles were maintained free-floating in culture medium and were grown in the absence of epidermis, dermis, subcutis, sebaceous glands, and other resident skin cells. Indications are accumulating that the epidermis (11,12), mast cells (24)(25)(26), macrophages (27,28), or other local immunological factors (2,10,29) and the local production of peptide hormones by sebaceous glands (30) might contribute to the regulation of hair growth. Our results indicate that the collagen-containing gelatin sponge matrix is also important in the long-term growth and viability of follicle cells.…”

Section: Resultsmentioning

confidence: 99%

“…The hair follicle, therefore, can also serve as a fascinating model for studying tissue interactions and tissue remodeling under physiological conditions. It is a still-underappreciated model system for experimental analysis of a plethora of key questions relevant to developmental biology, endocrinology, chronobiology, pigment cell biology, and molecular genetics (1)(2)(3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Hair shaft elongation, follicle growth, and spontaneous regression in long-term, gelatin sponge-supported histoculture of human scalp skin.

Margolis

Paus

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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In order to better understand the molecular mechanisms of human hair growth control and to test hair growth-modulatory drugs, appropriate in vitro models are required. Here, we report the long-term growth, shaft elongation, and spontaneous regression of human hair follicles in histoculture of intact scalp skin. Human scalp skin with abundant hair follicles in various stages ofthe hair growth cycle was grown for up to 40 days in a gelatin sponge-supported histoculture system at the air/liquid interface. Isolated follicles placed in the gelatin-sponge matrix also supported hair shaft elongation, with the hair follicle cells remaining proliferative and viable for very long periods. Hair shaft elongation occurred mainly during the first 10 days of histoculture of both intact skin and isolated follicles. However, hair follicles were viable and follicle keratinocytes continued to incorporate [3H]thymidine for up to several weeks after shaft elongation had ceased as shown by fluorescent-dye double staining, measured by confocal laser scanning microscopy, and by histological autoradiography of [3H]thymidine incorporation, respectively.Hair follicles could continue their cycle in histoculture; for example, apparent spontaneous catagen induction was observed both histologically and by the actual regression of the hair follicle. In addition, vellus follicles were shown to be viable at day 40 after initiation of culture. In the histocultured human scalp we demonstrated the association ofmast cells with anagen follicles and macrophages with catagen follicles, suggesting a role of these cells in the hair cycle. This histoculture technique should serve as a powerful tool for future hair research in the human system as well as a screening assay for compounds that can perturb the hair cycle.The clinical, social, and psychological significance of disorders of hair growth and the associated economic aspects are strong incentives to elucidate the control apparatus for follicle growth and cycling. The formation, shedding, and regrowth ofpigmented hair shafts result from tightly controlled, developmentally regulated epithelial-mesenchymal-neuroectodermal interactions in a unique miniorgan: for the entire life-span of the mammalian organism, it switches rhythmically from stages of resting (telogen) to stages of growth (anagen) and, via a short regression phase (catagen), back to resting (1). The hair follicle, therefore, can also serve as a fascinating model for studying tissue interactions and tissue remodeling under physiological conditions. It is a still-underappreciated model system for experimental analysis of a plethora of key questions relevant to developmental biology, endocrinology, chronobiology, pigment cell biology, and molecular genetics (1-7).Despite several decades of hair research, most of the basic mechanisms controlling hair growth and cycling have remained elusive. Since several rodent models are available for studying hair follicle growth in vivo and in vitro (e.g., refs.

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A Biologist'S Reflections on Dermatology

Cited by 69 publications

References 35 publications

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Hair shaft elongation, follicle growth, and spontaneous regression in long-term, gelatin sponge-supported histoculture of human scalp skin.

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