Dysregulation of melanocyte function by Th17‐related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris

Kotobuki, Yorihisa; Tanemura, Atsushi; Yang, Lingli; Itoi, Saori; Wataya‐Kaneda, Mari; Murota, Hiroyuki; Fujimoto, Minoru; Serada, Satoshi; Naka, Tetsuji; Katayama, Ichiro

doi:10.1111/j.1755-148x.2011.00945.x

Cited by 136 publications

(158 citation statements)

References 41 publications

(62 reference statements)

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“…Immunofluorescent staining for CD4 (green), IL-17A (red), CD8 (red) and FOXP3 (red)was performed as previously described [11,12]. Briefly, paraffin-embedded archival tissues were deparaffinized in absolute xylene and dehydrated in a sequential ethanol dilution series.…”

Section: Methods Cases and Resultsmentioning

confidence: 99%

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Alopecia Areata: Infiltration of Th17 Cells in the Dermis, Particularly around Hair Follicles

et al. 2013

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Background: The precise pathogenesis of alopecia areata remains unknown, although this disease seems to be triggered by helper T cell infiltration in hair follicles. Recent studies of psoriasis and vitiligo have demonstrated the involvement of Th17 cells. Psoriasis and vitiligo occasionally develop concomitantly or inversely in patients with alopecia areata. Objective: The aim of this study was to determine whether Th17 cells are present in the affected lesions of alopecia areata. Methods: We performed immunofluorescent staining of representative immunocompetent cells that had infiltrated into the skin of the scalp in 4 individuals with alopecia areata (single patchy alopecia areata, multiple patchy alopecia areata, alopecia totalis and alopecia universalis). Results: We found the infiltration of CD4⁺IL-17A⁺ Th17 cells in the dermis, particularly around hair follicles, in all 4 cases. Conclusions: These findings suggest the possibility that alopecia areata is induced by a Th17 cell-associated autoimmune mechanism.

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Section: Methods Cases and Resultsmentioning

confidence: 99%

“…Recent studies show that psoriasis and vitiligo are mediated by the lineage of Th17 cells [9,10,11,12]. Naive CD4 + helper T cells can be induced toward Th17 cells via the stimulation of interleukin (IL)-6 and IL-1β and tumor growth factor-β [13].…”

Section: Introductionmentioning

confidence: 99%

Alopecia Areata: Infiltration of Th17 Cells in the Dermis, Particularly around Hair Follicles

et al. 2013

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“…Many of the currently identified cytokines can be produced by keratinocytes, including IL-1, -6, -7, -8, -10, -12, -15, -18, and -20, tumor necrosis factor (TNF) a and interferons (IFN) a, b and c [18]. Cytokine imbalance appears in the skin of vitiligo patients [19], such as IFN-c, IL-10, IL-13 and IL-17 [20,21] treatment of vitiligo with topical tacrolimus involved the unique immunosuppressive actions of IL-10. They demonstrated tacrolimus increased IL-10 expression in vitiligo lesions, and thereby inhibited melanocyte destruction triggered by Th1 pathways [22].…”

Section: Introductionmentioning

confidence: 99%

Interleukin 10 protects primary melanocyte by activation of Stat-3 and PI3K/Akt/NF-κB signaling pathways

et al. 2016

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“…18,24,25) Beyond that, in the case of vitiligo, an immune response is thought to be responsible for the destruction of normal melanocytes. 26) UV radiation causes skin pigmentation partly by inflammation, which is mediated by chemokines and cytokines secreted by cells neighboring melanocytes including keratinocytes, fibroblasts, or inflammatory cells in the skin. As reported, IFN-γ plays a role in inflammation-associated pigmentary changes in vivo.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

Zhou

Ling

Ping

2016

Biological & Pharmaceutical Bulletin

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Interferon-γ (IFN-γKey words interferon-γ (IFN-γ); 5-hydroxytryptamine (5-HT); cross-talk; melanogenesis; migration Skin is the largest organ in human body, which plays a role as biologically active barrier to the external environment. It acts not only as a target for neuroendocrine signals but also a source of hormones and neurotransmitters, particularly the epidermis.1) Epidermis and dermis are the two main parts of skin. Epidermal melanocytes, derived from the neural crest, can produce melanin to absorb ultraviolet radiation and provide photoprotection.2) Melanin is synthesized in melanosomes, which are specialized lysosomerelated organelle (LRO) of pigment cells devoting to the biosynthesis, storage and transport of melanin.3) Melanosomes undergo 4 maturation stages, each characterized by unique ultrastructural morphology and melanin content. 4,5) The principal role of the melanocyte is to produce the pigment within melanosomes and to transfer these organelles to upwards of 40 keratinocytes, which are neighboring melanocyte to constitute the 'epidermal melanin unit.' Melanocyte transport melanosomes from the formation site in the cell center to the principal site of transfer at dendritic tips. Accomplishing this feat, melanocyte needs to couple long-range, bidirectional microtubule-dependent transport of melanosomes along the length of dendrites with the capture and local movement of the organelles in actin-rich dendritic tips by the actin-based motor protein myosin Va. 5,6) Studies have shown that there are four possible mechanisms described for melanosome transfer, including the cytophagocytosis model, membrane fusion model, shedding-phagocytosis model and exocytosis-endocytosis model. 6) In addition, multifarious signaling pathways and transcription factors firmly manage melanocyte migration. These proteins and pathways provide and integrate signals to create the proper environment for its normal development and migration. 2)Melanin biosynthesis process is under a complex control mediated by multiple elements through different pathways. A series of pigment cell-specific melanosomal proteins are responsible for melanogenesis, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). 7-9) Skin cells can produce hormones, neurotransmitters and neuropeptides and corresponding functional receptors, owing to which constitute the cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis.10,11) It has recently uncovered that cutaneous expression of the biochemical machinery involved in the sequential transformation of L-tryptophan to serotonin and melatonin. 12,13) Serotonin 5-hydroxytryptamine (5-HT) is a neurotransmitter whose actions are mediated via an interaction with receptors, including seven families (5-HT 1-7 receptors) with at least 21 subtypes. Skin cells express mRNA encoding 5-HT receptors, 5-HT 1A, -1B, -2A, -2B, -2C, and -7 receptor.14,15) 5-HT 2A receptor was reported participating in the regulatory processes of 5-HT on melanogenesis.16) Our preli...

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Dysregulation of melanocyte function by Th17‐related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris

Cited by 136 publications

References 41 publications

Alopecia Areata: Infiltration of Th17 Cells in the Dermis, Particularly around Hair Follicles

Alopecia Areata: Infiltration of Th17 Cells in the Dermis, Particularly around Hair Follicles

Interleukin 10 protects primary melanocyte by activation of Stat-3 and PI3K/Akt/NF-κB signaling pathways

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

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