Mika Watanabe

Type XVII collagen coordinates proliferation in the interfollicular epidermis

Type XVII collagen (COL17) is a transmembrane protein located at the epidermal basement membrane zone. COL17 deficiency results in premature hair aging phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17 plays a central role in regulating interfollicular epidermis (IFE) proliferation. Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt signaling. Physical aging abolishes membranous COL17 in IFE basal cells because of inactive atypical protein kinase C signaling and also induces epidermal hyperproliferation. The overexpression of human COL17 in aged mouse epidermis suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE proliferation of neonatal and aged skin in distinct ways. Our study indicates that COL17 could be an important target of anti-aging strategies in the skin. DOI: http://dx.doi.org/10.7554/eLife.26635.001

Cutaneous Manifestations of Helicobacter cinaedi Infection

Helicobacter cinaedi causes gastroenteritis and bacter-aemia, particularly in immunocompromised individuals. Although cellulitis is sometimes reported to accompany infection by this pathogen, the cutaneous manifestations are poorly understood. To clarify the characteristic cutaneous features, 47 cases of H. cinaedi bacteraemia experienced at Sapporo City General Hospital as nosocomial infection were retrospectively evaluated. Thirty-four percent (16 cases) of the patients showed cutaneous lesions. They all had sudden onset of erythemas accompanied by high temperature. The most common cutaneous manifestations were found to be superficial cellulitis, which results in painful erythemas or infiltrated erythematous plaques on the extremities. These skin lesions can be an early clinical indicator of H. cinaedi bacteraemia in the setting of nosocomial infection.

Development of bullous pemphigoid during treatment of psoriatic onycho-pachydermo periostitis with ustekinumab.

Ustekinumab is a human monoclonal antibody that specifically binds to the p40 subunit of interleukin (IL)‐12 and IL‐23, inhibiting the activity of both cytokines, thereby blocking the T‐helper (Th)1 and Th17 inflammatory pathways. While biologic agents have dramatically changed the strategies of psoriasis treatment, increasing cases of autoimmune diseases during the use of such agents have been reported. We experienced a case of bullous pemphigoid occurring during treatment of a rare variant of psoriatic arthritis, psoriatic onycho‐pachydermo periostitis with ustekinumab. Only six cases of autoimmune blistering diseases during treatment with biologic agents have ever been reported including our case, and we herein review the published work of these cases. Dermatologists must be attentive to the possibility of autoimmune blistering diseases during ustekinumab treatment.

Generalized acute subcutaneous edema as a rare cutaneous manifestation of severe dermatomyositis

References 1 Godar DE, Urbach F, Gasparro FP, van der Leun JC. UV doses of young adults. Photochem Photobiol 2003; 77: 453–457. 2 Balato N, Gaudiello F, Balato A, Monfrecola G. Sun habits in the children of Southern Italy. J Am Acad Dermatol 2007; 57: 883–887. 3 Stinco G, Favot F, Quinkeinstein E, Zanchi M, Valent F, Patrone P. Children and sun exposure in the Northeast of Italy. Pediatr Dermatol 2005; 22: 520–524. 4 Ruggiero G, Gelmetti C, Adamo MC et al. Atopic dermatitis (AD) management in an Italian pediatric clinic. G Ital Dermatol Venereol 2012; 147: 71–81. 5 Dietrich AJ, Olson AL, Sox CH, Winchell CW, Grant-Petersson J, Collison DW. Sun protection counseling for children: primary care practice patterns and effect of an intervention on clinicians. Arch Fam Med 2000; 9: 155–159. 6 Smith BJ, Ferguson C, McKenzie J, Bauman A, Vita P. Impacts from repeated mass media campaigns to promote sun protection in Australia. Health Promot Int 2002; 17: 51–60. 7 Gritz ER, Tripp MK, de Moor CA, Eicher SA, Mueller NH, Spedale JH. Skin cancer prevention counseling and clinical practices of pediatricians. Pediatr Dermatol 2003; 20: 16–24. 8 Balk SJ, O’Connor KG, Saraiya M. Counseling parents and children on sun protection: a national survey of pediatricians. Pediatrics 2004; 114: 1056–1064. 9 Mah e E, Assathiany R, Fay-Chatelard F. et al. Counselling on sun protection, a survey of French paediatricians. J Eur Acad Dermatol Venereol 2013; 27: e424–e427. 10 Badosa J, Calb o J, Mckenzie R et al. Two methods for retrieving UV index for all cloud conditions from sky imager products or total SW radiation measurements. Photochem Photobiol 2014; 90: 941–951.

Loss of interaction between plectin and type XVII collagen results in epidermolysis bullosa simplex

Plectin is a linker protein that interacts with intermediate filaments and β4 integrin in hemidesmosomes of the epidermal basement membrane zone (BMZ). Type XVII collagen (COL17) has been suggested as another candidate plectin binding partner in hemidesmosomes. Here, we demonstrate that plectin–COL17 binding helps to maintain epidermal BMZ organization. We identified an epidermolysis bullosa (EB) simplex patient as having markedly diminished expression of plectin and COL17 in skin. The patient is compound heterozygous for sequence variants in the plectin gene (PLEC); one is a truncation and the other is a small in‐frame deletion sequence variant. The in‐frame deletion is located in the putative COL17‐binding domain of plectin and abolishes the plectin–COL17 interaction in vitro. These results imply that disrupted interaction between plectin and COL17 is involved in the development of EB. Our study suggests that protein–protein binding defects may underlie EB in patients with unidentified disease‐causing sequence variants.

Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita

Type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone, has been characterized as a defective protein in dystrophic epidermolysis bullosa and as an autoantigen in epidermolysis bullosa acquisita. Although COL7 is produced and secreted by both epidermal keratinocytes and dermal fibroblasts, the role of COL7 with regard to the epidermis is rarely discussed. This review focuses on COL7 physiology and pathology as it pertains to epidermal keratinocytes. We summarize the current knowledge of COL7 production and trafficking, its involvement in keratinocyte dynamics, and epidermal carcinogenesis in COL7 deficiency and propose possible solutions to unsolved issues in this field.

Thymoma-associated multi-organ autoimmunity: two cases and a review of the literature.

Thymoma-associated multi-organ autoimmunity (TAMA) is defined as a disease of the liver, intestine, and skin, which histopathologically resembles graft-versus-host disease (GVHD).1,2 Several sporadic cases imply that cutaneous manifestations of TAMA are associated with a poor prognosis.2-5 However, it is difficult to examine the association because of the rarity of the disease. Herein we describe two cases of TAMA with cutaneous lesions and fatal courses, and review the literature with a focus on the prognosis. This article is protected by copyright. All rights reserved.

Psoriatic onycho‐pachydermo‐periostitis progressing to generalized pustular psoriasis

associated with the buttons, studs or belts of jeans, but detectable levels of nickel may disappear after washing of the garment at home, thereby improving the symptoms and complicating the history. Although our patient had symptoms correlating with a new item of clothing, there had been no improvement even after the item had been washed several times. As an intermediate in the production of diazo dyes, aminoazobenzene is known to cause clothing-related contact dermatitis, particularly with footwear. Cross-sensitivity between azo dyes and para-amino compounds such as PPD is well described, and can represent either true crossreaction or simultaneous positive reactions of variable clinical significance. Although not the most common sensitizing antraquinone dye, Disperse blue 35 is also a known cause of clothing-related contact allergy. When confronted by a classic presentation strongly suggestive of nickel allergy, it may be tempting to defer patch testing, assume the common allergen is at fault, and give empirical avoidance advice. However, this case demonstrates the importance of thorough history-taking, correlating symptoms to exposure and patch testing to the patient s own products, without which the cause would not have been found. To our knowledge, no other cases of non-nickel button dermatitis have been reported. We stress that even when confronted with a classic nickel dermatitis, patch testing is advisable.

Life before and beyond blistering: The role of collagen XVII in epidermal physiology.

Type XVII collagen (COL17) is a transmembranous protein that is mainly expressed in the epidermal basal keratinocytes. Epidermal‐dermal attachment requires COL17 expression at the hemidesmosomes of the epidermal basement membrane zone because congenital COL17 deficiency leads to junctional epidermolysis bullosa and acquired autoimmunity to COL17 induces bullous pemphigoid. Recently, in addition to facilitating epidermal‐dermal attachment, COL17 has been reported to serve as a niche for hair follicle stem cells, to regulate proliferation in the interfollicular epidermis and to be present along the non‐hemidesmosomal plasma membrane of epidermal basal keratinocytes. This review focuses on the physiological properties of COL17 in the epidermis, its role in maintaining stem cells and its association with signalling pathways. We propose possible solutions to unanswered questions in this field.

Interplay between epidermal stem cell dynamics and dermal deformation

Tissue growth is a driving force of morphological changes in living systems. Whereas the buckling instability is known to play a crutial role for initiating spatial pattern formations in such growing systems, little is known about the rationale for succeeding morphological changes beyond this instability. In mammalian skin, the dermis has many protrusions toward the epidermis, and the epidermal stem cells are typically found on the tips of these protrusions. Although the initial instability may well be explained by the buckling involving the dermis and the basal layer, which contains proliferative cells, it does not dictate the direction of these protrusions, nor the spatial patterning of epidermal stem cells. Here we introduce a particle-based model of self-replicating cells on a deformable substrate composed of the dermis and the basement membrane, and investigate the relationship between dermal deformation and epidermal stem cell pattering on it. We show that our model reproduces the formation of dermal protrusions directing from the dermis to the epidermis, and preferential epidermal stem cell distributions on the tips of the dermal protrusions, which the basic buckling mechanism fails to explain. We argue that cell-type-dependent adhesion strengths of the cells to the basement membrane are crucial factors influencing these patterns.Epidermal renewal: How cells find their placeOur epidermis loses 1.8 million skin cells per hour. This loss is balanced by the generation of new cells at the epidermal-dermal interface, the basement membrane, which features characteristic dermal protrusions. A team led by Masaharu Nagayama at Hokkaido University in Japan emulates epidermal renewal using a particle-based model. Using this approach, the authors uncover that constant cell division leads to crowding at the basement membrane. Depending on the energy cost, cells will either detach from the membrane or can be accommodated by deforming the membrane, thereby forming dermal protrusions. The model also explains observations that stem cells are preferentially found at the tips of these protrusions. The model does not rely on external signals from the dermis and could serve as a generic mechanism to other pattern-forming systems.