Alopecia Areata in Aging C3H/HeJ Mice

Sundberg, John P.; Cordy, Wade R; King, Lloyd E.

doi:10.1111/1523-1747.ep12382416

Cited by 167 publications

(148 citation statements)

References 27 publications

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“…Although having some similarity in appearance to that of alopecia areata described in aging C3H/HeJ mice, 43 the clinical and histologic findings in our model of ADlike lesions differ significantly from those seen in mice with spontaneous alopecia. The hair loss in spontaneous alopecia typically develops diffusely or in circular areas on the dorsal surface of mice beginning at 6 to 8 months of age.…”

Section: Discussioncontrasting

confidence: 39%

“…Microscopic examination of plucked hair from both mice with AD-like lesions and naive mice showed no evidence of parasitic infestation. In addition, skin cultures for aerobic and anaerobic bacteria 43 showed no evidence of pathogenic organisms. This is the first murine model of AD-like lesions induced by oral sensitization with a food protein.…”

Section: Discussionmentioning

confidence: 95%

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Murine model of atopic dermatitis associated with food hypersensitivity

Kleiner²,

Huang³

et al. 2001

Journal of Allergy and Clinical Immunology

110

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Background: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 12% of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4 + T H 2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. Objective: The purpose of this study was to establish a murine model of food-induced AD. Methods: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. Atopic dermatitis (AD) is a form of eczema that generally begins in early infancy and is characterized by extreme pruritus, chronically relapsing course, and distinctive distribution. AD is often the first sign seen in a child who is prone to atopic disease, with 50% of all AD developing in the first year of life and 80% developing by 5 years of age. 1 In chronic skin lesions the epidermis has moderate-to-marked hyperplasia, with elongation of the rete ridges and prominent hyperkeratosis. Spongiosis is variable, and the numbers of mast cells and Langerhans cells are significantly increased. 2,3 Eosinophils are sparse, although eosinophil products (major basic protein) are prominent. 4 Although the pathogenic role of allergy in AD has been debated for over a century, clinical studies over the past 2 decades have supported the pathogenic role of food allergy in a subset of patients with AD. 5-7 A recent study found that approximately 40% of children with moderate-to-severe AD attending a university dermatology clinic had food hypersensitivity. 7 Other studies delineating the role of IgE-bearing antigen-presenting cells in establishing T H 2 lymphocytic responses 8 and demonstrating the predominant T H 2-lymphocytic infiltrate in acute eczematous lesions 9 have provided further support for the pathogenic role of allergy in AD.Animal models provide powerful tools for dissecting pathogenic mechanisms responsible for various disorders. A number of murine models of asthma have been developed in the past several years that have contributed greatly to our understanding of the immunopathogenesis of allergen-induced asthma. 10-12 Models of antigenassociated AD have been reported in cats and dogs, but because of difficulties with consistent induction of ADlike eruptions and high expense, they have not been widely studied. 13,14 A mouse strain, NC/Nga, has been reported that spontaneously has an AD-like skin lesion and IgE hyperproduction, presumably triggered by environmental factors. 15 More recently, a murine model of AD was described in which BALB/c mice were sensitized to ovalbumin (OVA...

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Section: Discussioncontrasting

confidence: 39%

Section: Discussionmentioning

confidence: 95%

Murine model of atopic dermatitis associated with food hypersensitivity

Kleiner²,

Huang³

et al. 2001

Journal of Allergy and Clinical Immunology

110

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“…Accordingly, in the C3H/HeJ mouse model for AA, Treg alterations have been observed in the skin and in draining lymph nodes [11]. Treg are commonly identified by the intracellular expression of forkhead box P3 transcription factor (FOXP3) that controls their development and function [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

et al. 2012

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Alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles, is associated with polymorphisms in immune-related genes and with decreased number of CD4? CD25? T regulatory cells (Treg). Treg function is modulated by the forkhead box protein 3 (FOXP3) transcription factor and by inducible costimulator (ICOS), through interaction with the relative ligand, ICOSLG, whose genes are polymorphic. The aim of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) of the rs2294020 FOXP3 and/ or rs378299 ICOSLG genes may be associated with AA. A case-control study was performed in 120 AA patients and 84 controls. SNPs were analyzed by gene sequencing. FOXP3 and ICOSLG gene expressions were analyzed by real-time PCR. Increased frequencies of the genotype carrying the FOXP3 rs2294020-3675(A) [P = 0.002, OR (95 % CI): 2.55 (1.2-2.7)] or the ICOSLG rs378299-509(C) [P = 0.01, OR (95 % CI): 2.21 (1.1-2.6)] allelic variants were observed in AA patients than in controls. The genotype carrying the combination of the FOXP3 rs2294020-3675(A) and ICOSLG rs378299-509(C) allelic variants with the HLA DQB1*03 allele was more frequently present in AA patients than in controls (P = 0.04). The presence of the FOXP3 rs2294020-3675(A) or the I-COSLG rs378299-509(C) allelic variant was associated with reduced relative gene expression in AA patients. These data suggest that rs2294020 SNP of FOXP3 gene and rs378299 SNP of ICOSLG gene are associated with AA and with a reduced expression of the FOXP3 and ICOSLG genes in alopecia patients.

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“…As a model, we choose alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles resulting in hair loss [30,31]. The human disease is closely mimicked by C3H/HeJ mice that develop AA spontaneously, or after the transfer of full thickness skin grafts [32].…”

Section: Introductionmentioning

confidence: 99%

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

2006

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CD44 is involved in leukocyte migration and activation and has recently been reported to contribute to leukocyte extravasation by associating with CD49d. We explored whether similar changes in CD44 activity are seen in vivo using murine alopecia areata (AA) as a chronic, organ‐related autoimmune disease model system. Expression of the activated, hyaluronan‐binding form of CD44, and of CD49d, was elevated in draining lymph node cells (LNC) of AA‐affected mice as compared to control mice. LNC of AA mice displayed increased motility, proliferative activity and apoptosis resistance, which were equally well inhibited by anti‐CD44 and anti‐CD49d. The latter is the sequelae of the association between CD44 and CD49d that is seen in activated lymphocytes. Significantly, due to CD44‐CD49d complex formation, CD44 gains access to focal adhesion kinase and CD49d gains access to CD44‐associated lck and ezrin, such that downstream kinases become activated via CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually avail themselves of the partner's signaling pathways and the ligand binding of each one triggers signaling pathways of both. This strongly influences the lymphocytes’ activation state and function.

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Alopecia Areata in Aging C3H/HeJ Mice

Cited by 167 publications

References 27 publications

Murine model of atopic dermatitis associated with food hypersensitivity

Murine model of atopic dermatitis associated with food hypersensitivity

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

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