Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition

Xing, Luzhou; Dai, Zhijun; Jabbari, Ali; Cerise, Jane E.; Higgins, Claire A.; Gong, Wei; Jong, Annemieke de; Harel, Sivan; DeStefano, Gina M.; Rothman, Lisa; Singh, Pallavi; Petukhova, Lynn; Mackay‐Wiggan, Julian; Christiano, Angela M.; Clynes, Raphael

doi:10.1038/nm.3645

Cited by 767 publications

(945 citation statements)

References 28 publications

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“…Recently it was shown that systemically administered pharmacological inhibitors of Janus kinase (JAK) family of protein tyrosine kinases, as downstream efectors of the IFN-γ and γc cytokine receptors, prevented the development of alopecia areata in a mouse model reducing the accumulation of efector T cells in the skin [63]. During the course of the study, the authors noticed unexpected regrowth of HFs after topical treatment with JAK-STAT inhibitors.…”

Section: Dermal Papilla Cells and Their Inductive Propertiesmentioning

confidence: 99%

Hair Follicle Reconstruction and Stem Cells

Kalabusheva¹,

Chermnykh²,

Terskikh³

et al. 2017

Hair and Scalp Disorders

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De novo hair follicle (HF) formation in embryonic skin and hair growth in postnatal skin are the result of epithelial-mesenchymal interactions between specialized mesenchymal dermal papilla (DP) and epithelial stem cells that give rise to hairs. Adult HF is a valuable source of diferent lineages of stem cells (SCs) with morphogenetic potential. Epithelial stem cells are residing in the special compartment of HF (the bulge) and can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. This review summarizes the current knowledge on key characteristics of HF SC populations in terms of regenerative potential. General biological principles that govern the mesenchymal-epithelial interactions within the HF and the signaling pathways that control HF development are discussed. The main focus is on recent approaches to reconstruct folliculogenesis in vitro and perspectives of the tissue engineering in alopecia therapy.

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Section: Dermal Papilla Cells and Their Inductive Propertiesmentioning

confidence: 99%

Hair Follicle Reconstruction and Stem Cells

Kalabusheva¹,

Chermnykh²,

Terskikh³

et al. 2017

Hair and Scalp Disorders

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“…Transfer of these cytotoxic cells from mice with alopecia areata induced alopecia areata in healthy mice; on the other hand, NKG2D+ T cell-depleted lymph node cells transferred from the diseased mice to the healthy mice did not cause any disease. Interferon produced by NKG2D+ T cell is thought to contribute to the loss of immune-privileged status of hair follicles [11].…”

Section: Pathogenesismentioning

confidence: 99%

Alopecia Areata

Engın¹,

Oba²,

Tüzün³

2017

Hair and Scalp Disorders

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Alopecia areata is an organ-specific autoimmune disease targeting hair follicles. It causes nonscarring hair loss. The prevalence rate of the disease is approximately 1 in 1000 people worldwide. The condition is most commonly seen as circular areas of hair loss, but it may sometimes be as extensive as to involve the whole scalp or whole body. The complex pathophysiology of alopecia areata involves an autoimmune basis. Association of alopecia areata with other autoimmune diseases, such as thyroiditis and vitiligo, and the good response of patients to immunosuppressive treatment support an autoimmune etiology. Although some poor prognostic signs are defined, the course of the disease is unpredictable and the response to treatment can be variable. To date, there are neither preventive nor curative measures to deal with the condition. First-line therapy for patchy disease is topical and intralesional steroids, whereas extensive disease is conventionally managed with immunotherapy. New treatment agents, such as excimer laser, low-dose recombinant interleukin 2, Janus kinase inhibitors, and simvastatin/ezetimibe, are promising.

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“…ey are considered to be involved in various skin disorders [82] including contact dermatitis, psoriasis, gra versus host disease, vitiligo, alopecia areata [86], and drug eruptions [87]. A er being primed by DCs, CD8 T cells circulate around the tissue having assumed a cytotoxic memory phenotype.…”

Section: T Cells T Cells In Their Naive State Rst Encounter Apcs In Smentioning

confidence: 99%

Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT)

Ono¹,

Kabashima²

2015

Allergo J

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Summarye skin is equipped with serial barriers that provide rapid and e cient protection against external intruders. Beneath the epidermal physical barriers of the stratum corneum and the tight junctions, the integrated immune systems in both the epidermis and the dermis act in a coordinated manner to protect the host.is "immunological" barrier is composed of various cells, including skin-resident cells, such as keratinocytes, dendritic cells, tissue-resident macrophages, resident memory T cells, mast cells, and innate lymphoid cells. Additionally, in ltrating memory T cells, monocytes, neutrophils, basophils, and eosinophils are recruited in support of the host immunity.In addition to discussing the role of each of these cellular populations, we describe the concept of skin associated lymphoid tissue (SALT), which reminds us that the skin is an important component of the lymphatic system. We further describe the newly discovered phenomenon of multiple cell gathering under skin in ammation, which can be referred to as inducible SALT (iSALT). iSALT contributes to our understanding of SALT by highlighting the importance of direct cell-cell interaction in skin immunity.Cite this as Ono S, Kabashima K. Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT). Allergo J Int 2015;24:170-9

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Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition

Cited by 767 publications

References 28 publications

Hair Follicle Reconstruction and Stem Cells

Hair Follicle Reconstruction and Stem Cells

Alopecia Areata

Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT)

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