Murine epidermal Langerhans cells and keratinocytes express functional P2X7 receptors

Please cite this paper as: Murine epidermal Langerhans cells and keratinocytes express functional P2X₇ receptors. Experimental Dermatology 2010; 19 : e151–e157. Abstract: Extracellular ATP via the activation of purinergic P2 receptors has an emerging role in cutaneous biology; however, the distribution of these receptors in mouse skin is poorly defined. This study investigated whether murine epidermal cell subpopulations express functional purinergic P2X₇ receptors. P2X₇ expression was examined by immunoblotting and immunofluorescence staining of epidermal cells from C57Bl/6 mice. P2X₇ function was evaluated by nucleotide‐induced ethidium⁺ uptake measurements in epidermal cells from C57Bl/6 mice, and from P2X₇ deficient mice and wild‐type littermate controls. P2X₇ was detected in whole epidermal cell preparations, and specifically on Langerhans cells (LCs) and keratinocytes (KCs). ATP induced ethidium⁺ uptake into LCs and KCs, with EC₅₀ values of 503 and 482 μm, respectively. BzATP, and to a lesser extent ATPγS and ADP, also induced ethidium⁺ uptake; while UTP, αβ‐meth‐ATP and NAD were ineffective. ATP‐induced ethidium⁺ uptake was impaired by Na⁺ and Mg²⁺, and the P2X₇ antagonist, A‐438079 and was absent in LCs and KCs from P2X₇ deficient mice. These results demonstrate that murine LCs and KCs express functional P2X₇, and support a role for this receptor in cutaneous biology.     

Subpopulation of murine epidermal Langerhans cells identified by lectin-binding sites

Summary Lectin-binding profiles of epidermal Langerhans cells (LCs) were investigated in three strains of mice using immunofluorescence procedures. Three lectin-binding profiles were observed in each strain of mice. Most epidermal LCs reacted with concanavalin A (Con A) and Ricinus communis agglutinin 1 (RCA-1), whereas none reacted with Dolichos biflorus agglutinin (DBA). Peanut agglutinin (PNA) and wheat germ agglutinin (WGA) reacted with some of the epidermal LCs. These binding profiles were similar from site to site of the body in all strains of mice. We also investigated the lectin-binding profiles of epidermal Ia positive (Ia⁺) cells migrating into the grafted skin up to 165 days after transplantation. BALB/c (H-2^d) murine skin was grafted onto the back of (C3H/He×BALB/c)F1 (H-2^k×H-2^d) mice. The percentages of migrating I-A⁺ epidermal cells reactive with PNA and WGA were different from those of the normal epidermis soon after grafting and reached a normal level at 43 days after grafting. Our results demonstrated that there is a heterogeneous population of epidermal LCs defined by lectin-binding profiles.     

Mast cells are required for phototolerance induction and scratching abatement

Dermal mast cells protect the skin from inflammatory effects of ultraviolet (UV) radiation and are required for UV‐induced immune suppression. We sought to determine a potential mechanistic role of mast cells in reducing the sensitivity to UV radiation (i.e. phototolerance induction) through photohardening. We administered single UV exposures as well as a chronic UV irradiation regime to mast cell‐deficient Kit^{W‐Sh/W‐Sh} mice and their controls. The chronic irradiation protocol was similar to that given for prophylaxis in certain photodermatoses in humans. Compared to controls, UV‐exposed Kit^{W‐Sh/W‐Sh} mice were more susceptible to epidermal hyperplasia and dermal oedema which was linked to blood vessel dilation. Unexpectedly, Kit^{W‐Sh/W‐Sh} mice exhibited an excessive scratching behaviour following broadband UVB plus UVA or solar simulated UV irradiation at doses far below their minimal skin‐swelling dose. Protection from this UV‐induced scratching phenotype was dependent on mast cells, as engraftment of bone marrow‐derived cultured mast cells abated it entirely. Kit^{W‐Sh/W‐Sh} mice were entirely resistant to phototolerance induction by photohardening treatment. Compared to controls, these mice also showed reduced numbers of regulatory T cells and neutrophils in the skin 24 h after UV irradiation. While it is well known that mast cell‐deficient mice are resistant to UV‐induced immune suppression, we have discovered that they are prone to develop photo‐itch and are more susceptible to UV‐induced epidermal hyperplasia and skin oedema.     

Down-regulation of Langerhans cell protein kinase C-β isoenzyme expression in inflammatory and hyperplastic dermatoses

The family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin. Ca²⁺-dependent PKC activity, PKC-β protein and epidermal Langerhans cell (LC) PKC-β immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-α and PKC-β expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-α and PKC-β, and the LC marker CDla, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-β and CDla by epidermal LCs. Analysis of the number of PKC-^β+ and CDl^a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL. the PKC-^β+ epidermal LC number was significantly reduced, whereas the CDl^a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-β+ and CDla⁺ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-β⁺ epidermal LC number was normal, and CDla⁺ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC⁺/CDla⁺ was reduced in all the dermatoses studied, suggesting activation of PKC-β, with subsequent down-regulation. Within the dermis, increased PKC-β staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC FKC-β occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (iii the pattern of epidermal LC PKC-β and CDla expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-β associated with reduced CDla⁺ epidermal LCs in allergic and irritant contact dermatitis suggests that PK.C-β may transduce the signal for migration of LCs from human epidermis.     

Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice

Summary Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1⁺ dendritic cells (Thy-1⁺DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (me ^v ), nude (nu), and rhino (rh ^hr ) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1⁺DEC. Although nude mice showed normal numbers of Thy-1⁺ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1⁺DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.This work was supported in part by grants from the US-Israel Binational Foundation for Science, the United States-Israel Bi-national Agricultural Research and Development Fund (BARD), the Foundation for the Study of Cell Biology and Molecular Virology, Phoenix, Arizona and United States Public Health Service grant CA-20408. E. S. is a fellow of the Foulkes Foundation, London, UK     

SNEVPrp19/PSO4 deficiency increases PUVA‐induced senescence in mouse skin

Senescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in vivo are still not well understood. SNEV^Prp19/PSO4 is a multifaceted protein, known to be involved in DNA damage repair and senescence, albeit only in vitro. In this study, we used heterozygous SNEV^+/− mice (SNEV‐knockout results in early embryonic lethality) and wild‐type littermate controls as a model to elucidate the role of SNEV^Prp19/PSO4 in DNA damage repair and senescence in vivo. We performed PUVA treatment as model system for potently inducing cellular senescence, consisting of 8‐methoxypsoralen in combination with UVA on mouse skin to induce DNA damage and premature skin ageing. We show that SNEV^Prp19/PSO4 expression decreases during organismal ageing, while p16, a marker of ageing in vivo, increases. In response to PUVA treatment, we observed in the skin of both SNEV^Prp19/PSO4 and wild‐type mice an increase in γ‐H2AX levels, a DNA damage marker. In old SNEV^Prp19/PSO4 mice, this increase is accompanied by reduced epidermis thickening and increase in p16 and collagenase levels. Thus, the DNA damage response occurring in the mouse skin upon PUVA treatment is dependent on SNEV^Prp19/PSO4 expression and lower levels of SNEV^Prp19/PSO4, as in old SNEV^+/− mice, result in increase in cellular senescence and acceleration of premature skin ageing.     

Aryl Hydrocarbon Receptor and Autophagy-Related Protein Microtubule-Associated Protein Light Chain 3 Expression in Psoriasis

BackgroundThe aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis. However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown.ObjectiveWe studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them.MethodsWe included 24 psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. AHR, CYP1A1, LC3, ATG5, BECN1 and Nrf2 mRNA levels were measured by quantitative polymerase chain reaction.ResultsAHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls.ConclusionAHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases.     

SVEP1 plays a crucial role in epidermal differentiation

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.     

A novel treatment option for photoaged skin

Background DNA damage as a result of ultraviolet (UV) exposure plays an important role in the progression of cutaneous aging. Both folic acid and creatine have been linked to the process of DNA protection and repair. Aims This study aims to investigate the effects of a commercially available folic acid– and creatine‐containing formulation to fight the clinical signs of premature skin aging. Patients/methods Both in vitro and in vivo home‐in‐use studies using a folic acid– and creatine‐containing formulation were performed aiming to elucidate the efficacy in terms of improvement of skin regeneration, protection from UV‐induced DNA damage (Comet assay), reduction of wrinkle volume, and skin visco‐elasticity. Furthermore, clinical evaluation and photography were carried out to determine the improvement of clinically graded parameters after treatment. Results Cultured full‐thickness epidermal skin models supplemented with folic acid and creatine after epithelial perturbation showed an accelerated skin regeneration compared to untreated control models. Similarly, application of a folic acid– and creatine‐containing formulation significantly improved epidermal turnover in vivo as evidenced by smaller corneocytes derived from the treated sites relative to the vehicle‐treated sides. In addition, topical in vivo application of this formulation significantly protected from UV‐induced DNA lesions, increased skin firmness, and reduced wrinkle volume compared to untreated control areas. Expert grading confirmed a significant decrease of fine and coarse wrinkles in the periocular region as well as overall wrinkles, tactile roughness, and laxity. Conclusions Taken together, these results show that the combination of folic acid and creatine significantly accelerates epidermal skin regeneration in vitro and in vivo. Together with the finding of improved biomechanical skin properties, we conclude that the described topical formulation provides an effective treatment option for (photo)‐aged skin.     

Developmental expression of C3 receptor on murine epidermal Langerhans cells during ontogeny

Summary The developmental expression of C3 receptor, an important surface marker of murine epidermal Langerhans cells (LCs), was quantitatively studied using an immunohistochemical technique on epidermal sheets and then compared with developmental expression of Ia antigen and membrane ATPase. Anti-Mac-1 monoclonal antibody associated with CR3 was used for detecting C3 receptor and proved positive for LCs by immunoelectron microscopy. Mac-1 positive (Mac-1⁺) cells showed quite a different distribution from those of ATPase⁺ and Ia⁺ cells. Almost the same number of Mac-1⁺ and ATPase⁺ cells were present during the embryonic period. The number of Mac-1⁺ cells gradually decreased from day 1 to day 5 of postnatal life, after which they increased again. Using the doublelabeling technique on epidermal sheets at day 1 of postnatal life, it was shown that Ia⁺ cells possessed membrane ATPase activity and some Mac-1⁺ cells expressed Ia antigen. On days 4 and 7 of postnatal life all Mac-1⁺ cells expressed Ia antigen. These findings suggest that Mac-1 antigen observed during the embryonic period gradually fades after birth and is re-expressed after day 5 of postnatal life.     

The effect of ageing on phenotype and function of monocyte-derived Langerhans cells

Background With increasing age the immune system shows functional decline. In the skin this is associated with an increased incidence of epidermal malignancies and infections. Epidermal Langerhans cells (LCs) act as sentinels of the immune system, recognizing, processing and presenting antigen and inducing T‐cell responses. Previous investigations have demonstrated a reduction in the number of epidermal LCs in elderly subjects. Moreover, the ability of LCs to migrate in response to tumour necrosis factor (TNF)‐α, but not interleukin (IL)‐1β, is significantly impaired in the elderly. Objectives To characterize further the changes in LC function that are associated with increasing chronological age, we have evaluated age‐related changes in the response of monocyte‐derived LCs (mLCs) to IL‐1β and TNF‐α. Methods The phenotype and function of mLCs were compared in six young (≤ 30 years) and six aged (≥ 70 years) healthy individuals using a combination of flow cytometry, cytokine and chemokine array, and a Transwell migration assay. Results Monocytes from aged individuals were able to differentiate into LCs. There were no significant differences in expression of activation markers, or in baseline or inducible cytokine secretion, by mLCs derived from aged or young subjects. Furthermore, migration in response to a chemokine ligand, CCL19, was equivalent in both age groups. Conclusions These data demonstrate that changes in LC function in the elderly are not associated with changes in systemic dendritic cell phenotype and function. Conditioning of LCs in situ by the epidermal microenvironment is likely to be more important.     

Immune escape phenomenon in molluscum contagiosum and the induction of apoptosis

Molluscum contagiosum (MC) may persist for many weeks, evading host immunity. We studied the mechanism of immune escape phenomenon in MC, and the possible inducer of apoptosis. Using tissue samples of MC, we examined the numbers of epidermal Langerhans cells (LC), the expression levels of macrophage inflammatory protein‐3α (MIP‐3α) and thymic stromal lymphopoietin (TSLP), and the apoptotic signals. After molluscum contagiosum virus (MCV) genotyping, we studied the expression of MCV‐encoded MC148 mRNA and MC159 mRNA which correspond to viral antagonist for CCR8 and viral Fas‐linked interleukin (IL)‐1β converting enzyme (FLICE)‐like inhibitor protein (vFLIP), respectively. The nutlin‐3‐induced apoptosis in MC was observed ex vivo. The numbers of CD1a⁺ or Langerin⁺ epidermal LC and the expression levels of MIP‐3α were markedly decreased in MC. The expression of TSLP was enhanced in the lesional epidermis of atopic dermatitis and human papillomavirus‐induced warts, whereas the expression was observed locally in MC. All 14 MC samples examined harbored MCV type 1. The MC148 mRNA was detected in all 14 samples and the MC159 mRNA was detected in 13 samples. Apoptotic cells were absent or at a background level in the living layers of MC, but their numbers were increased in the molluscum bodies by overnight incubation with 5 μmol/L nutlin‐3 in culture medium. In conclusion, molluscum bodies are protected from host immune responses and apoptotic signals by being surrounded by LC‐depleted epidermal walls and viral immunosuppressive molecules, but could be eradicated by reagents inducing p53‐dependent apoptosis.     

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands

To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5′ and 3′ untranslated region sequences (AREG‐UTR) led to a >10‐fold increase in hAREG expression compared to an otherwise‐identical construct containing only the coding region (AREG‐CDR). AREG‐UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG‐CDR mice. Histologically, AREG‐UTR mice presented with marked epidermal hyperplasia of tail skin (2.1‐fold increase in epidermal thickness with a 9.5‐fold increase in Ki‐67⁺ cells) accompanied by significantly increased CD4+ T‐cell infiltration. Dorsal skin of AREG‐UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG‐UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki‐67⁺ cells. To determine the response of AREG‐UTR animals to a pro‐inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG‐UTR and wild type mice (1.7‐ and 2.2‐fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen.     

Anti‐IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin‐deficient mice

Please cite this paper as: Anti‐IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin‐deficient mice. Experimental Dermatology 2010; 19: 252–258. Abstract: Sharpin‐deficient (Sharpin^cpdm) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil‐depletion in chronic inflammation, Sharpin^cpdm mice were treated with anti‐IL5 antibodies. Mice treated with anti‐IL5 had a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils after 10 days compared with sham‐treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti‐IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride‐binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation. Skin homogenates from mice treated with anti‐IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, kit ligand (Kitl) and Tgfa; and increased mRNA expression of Tgfb1, Mmp12 and tenascin C (Tnc). In order to further decrease the accumulation of eosinophils, Sharpin^cpdm mice were crossed with IL5 null mice. Il5^?/?, Sharpin^cpdm/Sharpin^cpdm mice had a 98% reduction of circulating eosinophils and a 95% decrease in cutaneous eosinophils compared with IL5‐sufficient Sharpin^cpdm mice. The severity of the lesions was similar between IL5‐sufficient and IL5‐deficient mice. Double mutant mice had a significant decrease in Abp1, and a significant increase in Tgfb1, Mmp12 and Tnc mRNA compared with controls. These data indicate that eosinophils are not essential for the development of dermatitis in Sharpin^cpdm mice and suggest that eosinophils have both pro‐inflammatory and anti‐inflammatory roles in the skin of these mice.     

Ultraviolet light induces Stat3 activation in human keratinocytes and fibroblasts through reactive oxygen species and DNA damage

Please cite this paper as: Ultraviolet light induces Stat3 activation in human keratinocytes and fibroblasts through reactive oxygen species and DNA damage. Experimental Dermatology 2010; 19: 654–660. Abstract: Stat3 is activated by the outer stressors, such as ultraviolet (UV) exposure. In this study, we investigated the Stat3 response to UV irradiation in human epidermal keratinocytes and dermal fibroblasts. Results indicated that UVB and UVC differentially activate Stat3 in these cells. The UV‐induced Stat3 activation was mediated by both reactive oxygen species (ROS) and DNA damage, and the dominancy of ROS and DNA damage to activate Stat3 depended on the wavelength of UV. By using fibroblasts from a patient with xeroderma pigmentosum A (XP‐A) and those transfected with human XPA gene, we found that UVB activates Stat3 via both ROS and DNA damage, while UVC does so mainly via DNA damage. The present data suggest that Stat3 activation in UV‐exposed human skin is one of the initial events where DNA damage and ROS are involved.     

Cryopeeling versus trichloroacetic acid peeling in the treatment of solar lentigines: Effect on epidermal Langerhans cells

Trichloroacetic acid (TCA) peeling may be effective in solar lentigines, but with concerns regarding potential tumorigenesis. Cryopeeling would be better with improving the whole sun‐damaged skin. We aimed to compare the efficacy and safety of cryopeeling and TCA 35% peeling for treatment of solar lentigines and assess their influence on the number of epidermal Langerhans cells (LC). Twenty‐five patients were treated with TCA 35% and cryopeeling on the right and left hands, respectively. Two sessions were done 3 weeks apart. Evaluations were scheduled at weeks 0, 3, and 6. Skin biopsies, taken before and after treatment, were evaluated histologically and immunohistochemically for the number of CD1a + epidermal LCs. Lentigines decreased after cryopeeling from the first session (p < .001), but after the second session with TCA peeling (p = .004). Cryopeeling produced significant lightening, compared with TCA (p = .015). Blistering, hyper/hypopigmentation were reported with cryopeeling, whereas only hyperpigmentation was noted after TCA peeling. The LCs remained at about the pretreatment number after cryopeeling (p = .058), though they decreased after TCA (p = .002). Cryopeeling provided faster and superior improvement of lentigines compared with TCA peeling. Furthermore, TCA seems to suppress LCs raising the concern for carcinogenic potential.     

Dermal infiltrates of cutaneous T‐cell lymphomas with epidermotropism but not other cutaneous lymphomas are abundant with langerin+ dendritic cells

Background The Langerhans cell (LC) hypothesis suggests that cutaneous T‐cell lymphomas (CTCL) are diseases of chronic T‐cell stimulation by LC‐mediated antigen presentation. Objective To investigate a broad panel of CTCL and cutaneous B‐cell lymphomas (CBCL) for the spatial association of langerin⁺ dendritic cells (DC) with T and B cells in the skin, respectively. Methods Fifty‐five specimens of CTCL and 10 of CBCL were double‐stained with monoclonal antibodies against langerin and CD3 or CD20, respectively, and evaluated by confocal laser scan microscopy. Results Dermal infiltrates in mycosis fungoides (n = 38), primary cutaneous CD4+ small/medium‐sized pleomorphic T‐cell lymphoma (n = 3) and primary cutaneous peripheral T‐cell lymphoma, unspecified (n = 3) were characterized by a high frequency of dermal langerin⁺ DCs. These cells were exclusively present in the malignant infiltrates. No direct co‐localization of CD3 and langerin could be resolved. Dermal langerin⁺ cells were detected only in one of six primary cutaneous anaplastic large cell lymphomas (C‐ALCL), characterized by epidermotropism. In other C‐ALCL cases (five of six), in lymphomatoid papulosis (n = 3), subcutaneous panniculitis‐like T‐cell lymphoma (n = 2), and all variants of CBCL no dermal langerin⁺ DCs could be found. Conclusions Langerin⁺ DCs are abundant in the dermal infiltrates of T‐cell lymphomas with specific involvement of the epidermis. This might indicate that immature LC and neoplastic T cells interact and gives rise to further studies to characterize the phenotype of the langerin⁺ cell population described here and its role in the pathology of CTCL.