Association between TLR1 polymorphisms and alopecia areata

Seok, Ho-Sik; Suh, Dong Woo; Jo, Byungchul; Lee, Hwang-Bin; Jang, Hye Sook; Park, Hun Kuk; Lew, Bark‐Lynn; Chung, Joo‐Ho; Sim, Woo‐Young

doi:10.3109/08916934.2014.910769

Cited by 20 publications

(14 citation statements)

References 46 publications

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“…First, the C3H/HeJ strain that has been used for almost all preclinical AA disease modeling carries a homozygous null mutant allele of the Tlr4 gene [78], while functionally equivalent Tlr4 mutations are not associated with human AA (as opposed to TLR1 poymorphisms [79]). However, even C3H/HeN mice, which are wild-type at the Tlr4 locus, are susceptible to an AA-like disease [56], suggesting that this peculiar TLR4 defect is not of major pathobiological relevance to the development of AA-like lesions in C3H/HeJ mice.…”

Section: Murine Models Of Aamentioning

confidence: 99%

Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies

Gilhar

Schrum

Etzioni³

et al. 2016

Autoimmunity Reviews

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One of the most common human autoimmune diseases, alopecia areata (AA), is characterized by sudden, often persisting and psychologically devastating hair loss. Animal models have helped greatly to elucidate critical cellular and molecular immune pathways in AA. The two most prominent ones are inbred C3H/HeJ mice which develop an AA-like hair phenotype spontaneously or after experimental induction, and healthy human scalp skin xenotransplanted onto SCID mice, in which a phenocopy of human AA is induced by injecting IL-2-stimulated PBMCs enriched for CD56+/NKG2D+ cells intradermally. The current review critically examines the pros and cons of the available AA animal models and how they have shaped our understanding of AA pathobiology, and the development of new therapeutic strategies. AA is thought to arise when the hair follicle’s (HF) natural immune privilege (IP) collapses, inducing ectopic MHC class I expression in the HF epithelium and autoantigen presentation to autoreactive CD8+ T cells. In common with other autoimmune diseases, upregulation of IFN-γ and IL-15 is critically implicated in AA pathogenesis, as are NKG2D and its ligands, MICA, and ULBP3. The C3H/HeJ mouse model was used to identify key immune cell and molecular principles in murine AA, and proof-of-principle that Janus kinase (JAK) inhibitors are suitable agents for AA management in vivo, since both IFN-γ and IL-15 signal via the JAK pathway. Instead, the humanized mouse model of AA has been used to demonstrate the previously hypothesized key role of CD8+ T cells and NKG2D+ cells in AA pathogenesis and to discover human-specific pharmacologic targets like the potassium channel Kv1.3, and to show that the PDE4 inhibitor, apremilast, inhibits AA development in human skin. As such, AA provides a model disease, in which to contemplate general challenges, opportunities, and limitations one faces when selecting appropriate animal models in preclinical research for human autoimmune diseases.

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Section: Murine Models Of Aamentioning

confidence: 99%

Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies

Gilhar

Schrum

Etzioni³

et al. 2016

Autoimmunity Reviews

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“…13,29 CD8+ lymphocytes are mainly responsible for follicular damage and predominate during activation of the disease, while CD4+ lymphocytes are fewer and only contribute together with CD8+ cells in the development of AA. Although It has been proposed that not only CD4+ and CD8+ lymphocytes are involved in these processes but also, natural killer cells, macrophages, Langerhans cells, and cytokines, 30,31 which could be generating three events: 1) an inflammatory process at the periphery of the patches, 2) an alteration of the hair follicle cycles, and 3) growth inhibition. 29 …”

Section: Immunological Factorsmentioning

confidence: 99%

Alopecia Areata. Current situation and perspectives

et al. 2017

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Alopecia areata (AA) is a dermatological disease characterized by non-scarring hair loss of the scalp and/or body, with an unpredictable and variable evolution in the patients in which, despite multidisciplinary efforts, its etiology is not entirely known, although some evidence suggests that environmental, immunological and genetic factors could be generating the disease. The aim of this review is to provide an updated panorama of the clinical characteristics, diagnosis and treatment of AA, to analyze the mechanisms that could participate in its etiology, as well as to review some of the most important genetic variants that could confer susceptibility to the development of this disease.

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“…Alopecia areata (AA), which is a common T lymphocyte cell‐mediated, organ‐specific autoimmune condition, is clinically described by different size and forms of nonscarring hair loss lesions on any hair‐bearing area . The prevalence of the disease is between 1% and 2% worldwide, and it takes place at any age from birth to late life .…”

Section: Introductionmentioning

confidence: 99%