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Medicinal Research Reviews Mar 2021Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation.... (Review)
Review
Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation. Genome-wide associated studies have identified single-nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background. Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, a minority of melanocyte demise, and melanocyte-specific antigens exposure. Of note, the self-responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo. The aberrantly heightened innate immunity, type-1-skewed T helper, and incompetent regulatory T cells tip the balance toward autoreaction and CD8 cytotoxic T lymphocytes finally execute the killing of melanocytes, possibly alarmed by resident memory T cells. In addition to the well-established apoptosis and necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, and necroptosis that are probably employed in melanocyte destruction. This review focuses on the various mechanisms of melanocytic death in vitiligo pathogenesis to demonstrate a panorama of that. We hope to provide new insights into vitiligo pathogenesis and treatment strategies by the review.
Topics: Apoptosis; CD8-Positive T-Lymphocytes; Humans; Melanocytes; Oxidative Stress; Vitiligo
PubMed: 33200838
DOI: 10.1002/med.21754 -
Nature Feb 2007Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute... (Review)
Review
Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution. Skin is the most common site of cancer in humans. Continued understanding of melanocyte contributions to skin biology will hopefully provide new opportunities for the prevention and treatment of skin diseases.
Topics: Animals; Hair Color; Humans; Melanocytes; Melanosomes; Receptor, Melanocortin, Type 1; Skin Neoplasms; Skin Pigmentation
PubMed: 17314970
DOI: 10.1038/nature05660 -
Expert Opinion on Therapeutic Targets Mar 2023The treatment of vitiligo remains challenging due to the complexity of its pathogenesis, influenced by genetic factors, oxidative stress and abnormal cell adhesion that... (Review)
Review
INTRODUCTION
The treatment of vitiligo remains challenging due to the complexity of its pathogenesis, influenced by genetic factors, oxidative stress and abnormal cell adhesion that collectively impact melanocyte survival and trigger immune system attacks, resulting in melanocyte death. Melanocytes in vitiligo are believed to exhibit genetic susceptibility and defects in cellular mechanisms, such as defects in autophagy, that reduce their ability to resist oxidative stress, leading to increased expression of the pro-inflammatory protein HSP70. The low expression of adhesion molecules, such as DDR1 and E-cadherin, accelerates melanocyte damage and antigen exposure. Consequently, autoimmune attacks centered on IFN-γ-CXCR9/10-CXCR3-CD8 T cells are initiated, causing vitiligo.
AREAS COVERED
This review discusses the latest knowledge on the pathogenesis of vitiligo and potential therapeutic targets from the perspective of suppressing autoimmune attacks and activating melanocytes functions.
EXPERT OPINION
Vitiligo is one of the most challenging dermatological diseases due to its complex pathogenesis with diverse therapeutic targets. Immune suppression, such as corticosteroids and emerging JAK inhibitors, has proven effective in disease progression. However, during the early stages of the disease, it is also important to optimize therapeutic strategies to activate melanocytes for alleviating oxidative stress and improving treatment outcomes.
Topics: Humans; Vitiligo; CD8-Positive T-Lymphocytes; Melanocytes; Oxidative Stress
PubMed: 36947026
DOI: 10.1080/14728222.2023.2193329 -
Current Opinion in Cell Biology Dec 2020Melanocytes are neuroectoderm-derived pigment-producing cells with highly polarized dendritic morphology. They protect the skin against ultraviolet radiation by... (Review)
Review
Melanocytes are neuroectoderm-derived pigment-producing cells with highly polarized dendritic morphology. They protect the skin against ultraviolet radiation by providing melanin to neighbouring keratinocytes. However, the mechanisms underlying melanocyte polarization and its relevance for diseases remain mostly elusive. Numerous studies have instead revealed roles for polarity regulators in other neuroectoderm-derived lineages including different neuronal cell types. Considering the shared ontogeny and morphological similarities, these lineages may be used as reference models for the exploration of melanocyte polarity, for example, regarding dendrite formation, spine morphogenesis and polarized organelle transport. In this review, we summarize and compare the latest progress in understanding polarity regulation in neuronal cells and melanocytes and project key open questions for future work.
Topics: Cell Differentiation; Cell Lineage; Cell Polarity; Humans; Keratinocytes; Melanocytes; Melanosomes; Neural Plate
PubMed: 33099084
DOI: 10.1016/j.ceb.2020.09.001 -
Pigment Cell & Melanoma Research Sep 2018Somatic stem cells are regulated by their niches to maintain tissue homeostasis and repair throughout the lifetime of an organism. An excellent example to study stem... (Review)
Review
Somatic stem cells are regulated by their niches to maintain tissue homeostasis and repair throughout the lifetime of an organism. An excellent example to study stem cell/niche interactions is provided by the regeneration of melanocytes during the hair cycle and in response to various types of injury. These processes are regulated by neighboring stem cells and multiple signaling pathways, including WNT/β-catenin, KITL/KIT, EDNs/EDNRB, TGF-β/TGF-βR, α-MSH/MC1R, and Notch signaling. In this review, we highlight recent studies that have advanced our understanding of the molecular crosstalk between melanocyte stem cells and their neighboring cells, which collectively form the niche microenvironment, and we focus on the question of how McSCs/niche interactions shape the responses to genotoxic damages and mechanical injury.
Topics: Animals; Humans; Melanocytes; Pigmentation; Signal Transduction; Stem Cell Niche; Stem Cells
PubMed: 29582573
DOI: 10.1111/pcmr.12701 -
Expert Opinion on Biological Therapy Nov 2014Melanocytes produce pigment granules that color both skin and hair. In the hair follicles melanocytes are derived from stem cells (MelSCs) that are present in hair... (Review)
Review
INTRODUCTION
Melanocytes produce pigment granules that color both skin and hair. In the hair follicles melanocytes are derived from stem cells (MelSCs) that are present in hair bulges or sub-bulge regions and function as melanocyte reservoirs. Quiescence, maintenance, activation and proliferation of MelSCs are controlled by specific activities in the microenvironment that can influence the differentiation and regeneration of melanocytes. Therefore, understanding MelSCs and their niche may lead to use of MelSCs in new treatments for various pigmentation disorders.
AREAS COVERED
We describe here pathophysiological mechanisms by which melanocyte defects lead to skin pigmentation disorders such as vitiligo and hair graying. The development, migration and proliferation of melanocytes and factors involved in the survival, maintenance and regeneration of MelSCs are reviewed with regard to the biological roles and potential therapeutic applications in skin pigmentation diseases.
EXPERT OPINION
MelSC biology and niche factors have been studied mainly in murine experimental models. Human MelSC markers or methods to isolate them are much less well understood. Identification, isolation and culturing of human MelSCs would represent a major step toward new biological therapeutic options for patients with recalcitrant pigmentary disorders or hair graying. By modulating the niche factors for MelSCs, it may one day be possible to control skin pigmentary disorders and prevent or reverse hair graying.
Topics: Animals; Cell Differentiation; Hair; Hair Follicle; Humans; Melanocytes; Skin Diseases; Skin Pigmentation; Stem Cells
PubMed: 25104310
DOI: 10.1517/14712598.2014.935331 -
Developmental Biology May 2019Skin pigmentation is a powerful defense against ultraviolet irradiation. Particularly in humans, the body surface needs to be widely covered by protective pigmentation,... (Review)
Review
Skin pigmentation is a powerful defense against ultraviolet irradiation. Particularly in humans, the body surface needs to be widely covered by protective pigmentation, and melanocytes, a major lineage of neural crest derivatives, have evolved several maneuvers to transfer melanin pigment to the skin. Recent studies with embryonic melanocytes of chickens and mice have revealed sequential events mediated by melanocytes to maximize the skin coverage by pigmentation. These processes include the migration of melanocyte precursors in the embryo, the microscopic uniform spacing of individual melanocytes, and melanosome transfer from melanocytes to keratinocytes. In particular, in vivo/ex vivo live-imaging techniques of melanosome transfer and a quantitative method to evaluate the distribution patterns of melanocytes have greatly advanced our understanding of how a limited number of cells can implement a maximal coverage of the large surface area of a developing body.
Topics: Animals; Cell Movement; Chick Embryo; Chickens; Humans; Melanins; Melanocytes; Melanosomes; Mice; Models, Biological; Neural Crest; Skin Pigmentation
PubMed: 29698617
DOI: 10.1016/j.ydbio.2018.04.016 -
Seminars in Cell & Developmental Biology Feb 2009Utilization of adult stem cells in regenerative therapies may require a thorough understanding of the mechanisms that establish, recruit and renew the stem cell, promote... (Review)
Review
Utilization of adult stem cells in regenerative therapies may require a thorough understanding of the mechanisms that establish, recruit and renew the stem cell, promote the differentiation of its daughters, or how the stem cell is repressed by its target tissue. Regeneration of melanocytes in the regenerating zebrafish caudal fin, or following larval melanocyte-specific ablation, or recruitment of new melanocytes during pigment pattern metamorphosis each provides evidence for melanocyte stem cells (MSCs) that support the melanocyte pigment pattern. We discuss the mechanisms of MSC regulation provided from analysis of normal or mutant regeneration in each of these systems, including the implications drawn from evidence that regeneration does not simply recapitulate ontogenetic development. These results suggest that analysis of melanocyte regeneration in zebrafish will provide a fine scale dissection of mechanisms establishing or regulating adult stem cells.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Humans; Melanocytes; Metamorphosis, Biological; Models, Biological; Regeneration
PubMed: 18950723
DOI: 10.1016/j.semcdb.2008.09.007 -
Pigment Cell Research Aug 2001The epidermal-melanin unit is composed of one melanocyte and approximately 36 neighboring keratinocytes, working in synchrony to produce and distribute melanin. Melanin... (Review)
Review
The epidermal-melanin unit is composed of one melanocyte and approximately 36 neighboring keratinocytes, working in synchrony to produce and distribute melanin. Melanin is synthesized in melanosomes, transferred to the dendrite tips, and translocated into keratinocytes, forming caps over the keratinocyte nuclei. The molecular and cellular mechanisms involved in melanosome transfer and the keratinocyte-melanocyte interactions required for this process are not yet completely understood. Suggested mechanisms of melanosome transfer include melanosome release and endocytosis, direct inoculation ('injection'), keratinocyte-melanocyte membrane fusion, and phagocytosis. Studies of the keratinocyte receptor protease-activated receptor-2 (PAR-2) support the phagocytosis theory. PAR-2 controls melanosome ingestion and phagocytosis by keratinocytes and exerts a regulatory role in skin pigmentation. Modulation of PAR-2 activity can enhance or decrease melanosome transfer and affects pigmentation only when there is keratinocyte-melanocyte contact. Moreover, PAR-2 is induced by UV irradiation and inhibition of PAR-2 activation results in the prevention of UVB-induced tanning. The role of PAR-2 in mediating UV-induced responses remains to be elucidated.
Topics: Humans; Keratinocytes; Melanocytes; Melanosomes; Phagocytosis; Skin Pigmentation
PubMed: 11549105
DOI: 10.1034/j.1600-0749.2001.140402.x -
PloS One 2021Based on the assumption that some progenitor cells in an organ might reside in neighboring adipose tissue, we investigated whether melanocyte progenitor cells reside in...
Based on the assumption that some progenitor cells in an organ might reside in neighboring adipose tissue, we investigated whether melanocyte progenitor cells reside in human subcutaneous adipose tissue. First, we examined the expression of human melanoma black 45 (HMB45) and microphthalmia-associated transcription factor (MITF) in undifferentiated adipose-derived stem cells (ADSCs) by immunostaining, RT-PCR, and western blotting. These two markers were detected in undifferentiated ADSCs, and their expression levels were increased in differentiated ADSCs in melanocyte-specific culture medium. Other melanocytic markers (Melan A, MATP, Mel2, Mel EM, tyrosinase, KIT, and PAX3) were also detected at variable levels in undifferentiated ADSCs, and the expression of some markers was increased during differentiation into the melanocyte lineage. We further showed that ADSCs differentiated in melanocyte-specific culture medium localized in the basal layer and expressed tyrosinase and HMB45 in a 3D epidermal culture system. Melanin deposits were also induced by ultraviolet-light-B (UVB) irradiation. These results demonstrate that melanocyte progenitor cells reside in human subcutaneous adipose tissue and that these cells might have the potential to differentiate into mature melanocytes. Melanocyte and keratinocyte progenitors residing in human subcutaneous tissue can be used for the treatment of skin diseases and skin rejuvenation in the future.
Topics: Biomarkers; Cell Differentiation; Cell Line, Tumor; Dihydroxyphenylalanine; Down-Regulation; Epidermis; Gene Expression Regulation; Humans; Keratinocytes; Melanins; Melanocytes; Melanoma; Microphthalmia-Associated Transcription Factor; Models, Biological; Pigmentation; RNA, Small Interfering; Stem Cells; Subcutaneous Tissue
PubMed: 34432824
DOI: 10.1371/journal.pone.0256622