A New Humanized Mouse Model for Alopecia Areata

Gilhar, Amos; Keren, Aviad; Paus, Ralf

doi:10.1038/jidsymp.2013.11

Cited by 26 publications

(22 citation statements)

References 18 publications

(30 reference statements)

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“…Repeated attacks and truncation of the hair cycle ultimately leads to a miniaturized, exhausted and dystrophic, empty HF in a state specific to AA known as nanogen . Discovery of the role of cytotoxic NKG2D+ T cells in this process has led to the use of JAK inhibitors for the treatment of AA, as IFN‐γ and IL‐15 (crucial cytokines for NKG2D+ T‐cell survival) signal via the JAK‐STAT pathway . Recently, another subset of regulatory invariant NKT (iNKT) cells are postulated to suppress NKG2D+ T‐cell activity to promote regrowth and remission in AA .…”

Section: Hair Cycling In Human Diseasementioning

confidence: 99%

Immune cell regulation of the hair cycle

Wang

2020

Experimental Dermatology

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The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial‐mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

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Section: Hair Cycling In Human Diseasementioning

confidence: 99%

Immune cell regulation of the hair cycle

Wang

2020

Experimental Dermatology

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“…The collapse of HF‐IP is considered to be a critical step of AA induction, and type 1 inflammation is regarded as a key mediator of the autoimmune reactions in AA lesions. Th1 cytokines, interferon (IFN)‐α and IFN‐γ, are key cytokines that initiate the collapse of HF‐IP with the upregulation of MHC class I expression at the proximal outer root sheath (ORS) and matrix cells, and these IFNs also stimulate NKG2D + CD8 + Tc1 cells . In addition, Th1/Tc1 chemokines, such as CXCL9 and CXCL10, are upregulated at the proximal ORS and matrix cells in AA lesions.…”

Section: Introductionmentioning

confidence: 99%

CCR5 is a novel target for the treatment of experimental alopecia areata

Ito

Suzuki

Funakoshi

et al. 2020

J Cutaneous Imm & Allergy

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Background Alopecia areata (AA) is an organ‐specific and cell‐mediated autoimmune disease. Hair follicle autoantigens are disclosed to these autoreactive NKG2D+CD8+ T cells. A Th1 chemokine, CXCL10, is highly expressed on hair follicle keratinocytes and leads to the infiltration of CXCR3+ and CCR5+ Th1 or Tc1 cells around anagen hair follicles in AA lesions. Aim To evaluate CCR5 as a new candidate target for the treatment of experimental AA. Methods We initiated 7‐month‐old female C3H/HeJ mice with intracutaneous injections of lymph node (LN) cells, which were activated by IL‐2, IL‐7, IL‐15, and CD3/CD25 Dynabeads, from C3H/HeJ mice with spontaneous AA. Then, 330 μg/d of maraviroc, a negative allosteric modulator of the CCR5 receptor that is already used for treating patients with human immunodeficiency virus, was orally administrated for 28 days. Results We successfully treated the experimental AA lesions of C3H/HeJ mice with maraviroc. In addition, CCR5 blockade prevented the development of AA in activated T cell‐transferred C3H/HeJ mice. Interestingly, maraviroc‐treated C3H/HeJ mice with experimental AA showed improvement of hair loss lesions after 2 weeks. Immunohistological assessments and FACS analysis revealed a decreased number of CD4+CCR5+ and CD8+CCR5+ T cells in the lesions after maraviroc treatment. A real‐time horizontal chemotaxis assay showed that maraviroc significantly inhibited the chemotactic activity of CD8+ LN cells toward RANTES. Furthermore, CCR5 blockade prevented experimental AA development when compared to phosphate‐buffered saline. Conclusion CCR5 appears to be a promising new candidate target for the treatment of AA. CCR5 blockade may prevent the development of AA as well as improve AA lesions.

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“…Human scalp explants grafted onto severe combined immunodeficient (SCID) mice is another experimental model reported by Kyoizumi et al [106]. Recently, Gilhar et al [107] developed a new humanized mouse model of AA, by transplantation of healthy human scalp skin obtained from normal volunteers on to SCID mice. This was followed by intradermal injection of either autologous or allogeneic peripheral blood mononuclear cells, which had been cultured with a high dose of IL-2 and were enriched for NK group 2D-positive (NKG2D + ) and CD56 + cells.…”

Section: Aa Alopecia Totalis and Alopecia Universalismentioning

confidence: 99%

Drug discovery for alopecia: gone today, hair tomorrow

Santos

Avci

Hamblin

2015

Expert Opinion on Drug Discovery

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Introduction Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. Areas covered In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8+NK group 2D-positive (NKG2D+) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. Expert opinion The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.

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A New Humanized Mouse Model for Alopecia Areata

Cited by 26 publications

References 18 publications

Immune cell regulation of the hair cycle

Immune cell regulation of the hair cycle

CCR5 is a novel target for the treatment of experimental alopecia areata

Drug discovery for alopecia: gone today, hair tomorrow

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