Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin

The immunocytochemical identification and characterization of indigenous dermal dendritic cells (dermal dendrocytes) using a rabbit polyclonal antibody to clotting enzyme factor XIII subunit A (FXIIIa) was carried out on normal and inflamed human cutaneous tissue. The immunophenotype of FXIIIa positive dendritic cells was analysed with a panel of 18 monoclonal antibodies using immunoperoxidase and double immunofluorescence staining techniques. The antibody against FXIIIa detected highly dendritic dermal cells located particularly in the upper reticular and papillary dermis. Double fluorescence microscopy showed that FXIIIa positive cells were bone marrow derived (HLe-I+) and co-expressed monocyte, macrophage or antigen presenting cell markers (HLA-DR+, LFA-I+, HLA-DQ+, OKM5+, Mo I+, Mono-I+, Leu M3+). No labelling was obtained with cell markers for Langerhans cells (CDI), T lymphocytes (CD2), granulocytes (LeuMI) fibroblasts (Te7), intercellular adhesion molecule-I (ICAM-I) or endothelial cells (Factor VIII related antigen). Gamma interferon induced increased expression of HLA-DR and co-expression of ICAM-I on FXIIIa+ dermal dendritic cells in normal skin in organ culture. Moreover, in benign inflammatory dermatoses such as atopic eczema and psoriasis there was an increased number of FXIIIa+, DR+, ICAM-I+ cells in the upper dermis and foci of FXIIIa+ cells in the epidermis closely associated with lymphocytes. FXIIIa positive cells in human skin represent a specific population of bone-marrow dermal dendritic cells, distinct from Langerhans cells, that share some features common to mononuclear phagocytes (monocyte/macrophages). In addition, the detection of HLA-DQ on 48% of FXIIIa+ cells and the lack of OKMI in combination with high OKM5 expression suggests an antigen-presenting cell phenotype.     

Distribution of CD1a-positive cells in psoriatic skin during the evolution of the lesions

Normal skin and psoriatic lesions from 35 patients were investigated immunohistochemically with regard to the CD1a+ cell population (Langerhans' cells and indeterminate cells) in the epidermis as well as in the dermal infiltrate. In the normal-appearing skin, we found the regularly typical pattern of CD1a+ dendritic cells in suprabasal position, but in lesional skin of chronic psoriasis the CD1a+ cells were scattered in the acanthotic epidermis. In initial lesions, CD1a+ cells represent up to 50-60% of the infiltrating cells of the dermal compartment, in several cases being preferentially localized in the upper part of the papillar dermis close up to the epidermal CD1a+ cells in basal position, whereas in chronic psoriasis they represent less than 10%. These results suggest that in psoriasis vulgaris, CD1a+ cells actively migrate between the epidermis and the dermal vessels.     

Epitopes for CD1a, CD1b, and CD1c antigens are differentially mapped on Langerhans cells, dermal dendritic cells, keratinocytes, and basement membrane zone in human skin.

BACKGROUND: CD1 antigens are classified serologically into at least three groups, CD1a, CD1b, and CD1c, and many kinds of monoclonal antibodies are available for each subgroup of CD1 antigens. CD1a, CD1b, and CD1c antigens have been shown to be selectively and differentially expressed on epidermal Langerhans cells and dermal dendritic cells in normal human skin. OBJECTIVE: The objective was to further delineate the localization of epitopes of CD1 antigens in human skin. METHODS: We examined the immunoreactivity of 14 different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies) with the immunoperoxidase technique. We also studied the reactivity of NU-T2 (CD1b) antibody by immunogold electron microscopy. RESULTS: The epitopes for CD1a, CD1b, and CD1c antigens were differentially mapped on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in human skin. CONCLUSION: These CD1 antibodies may be useful to analyze the phenotypic alteration of immune and nonimmune cells in various skin diseases.     

Epitope mapping of CD1a, CD1b, and CD1c antigens in human skin: differential localization on Langerhans cells, keratinocytes, and basement membrane zone.

CD1 antigens are classified into at least three groups, CD1a, CD1b, and CD1c. In order to delineate the localization of epitopes of CD1 antigens in human skin, we examined the immunoreactivity of fourteen different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies). The epitopes for CD1a, CD1b, and CD1c are differentially localized on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in normal human skin.     

"Dermal dendritic cells" comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages

A key cell type of the resident skin immune system is the dendritic cell (DC), which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LCs), mainly in the epidermis, and dermal DCs (DDCs), in the dermis. Here, the lineage of DDCs was investigated using monoclonal antibodies and immunohistology. We provide evidence that "DDC" comprise at least two major phenotypic populations of dendritic-appearing cells, immature DC expressing CD1, CD11c and CD208; and macrophages expressing CD209, CD206, CD163, and CD68. These data suggest that dermal dendritic-appearing macrophages comprise a novel part of the innate immune response in the resident skin immune system.     

Adult variant of self-healing papular mucinosis in a patient with rheumatoid arthritis: predominant proliferation of dermal dendritic cells expressing CD34 or factor XIIIa in association with dermal deposition of mucin

According to a recent classification, self-healing papular mucinosis (SHPM) is a subtype of papular mucinosis (also known as lichen myxedematosus), which is in turn a type of idiopathic localized cutaneous mucinosis. SHPM tends to occur in children, but there have been a few reports of an adult type. We report a 70-year-old Japanese woman who presented with reddish, rice-kernel-sized papules of a few days' duration on her right arm. She had a 25-year history of rheumatoid arthritis, which had been well treated with a low dose of corticosteroid as well as some other medications. No paraproteinemia or thyroid dysfunction were observed. The eruptions spontaneously resolved within 2.5 months of onset. Histological findings showed a well-circumscribed mucinous stroma surrounded by dermal mesenchymal cells, such as fibroblast-like cells in the middle of the dermis. Immunohistochemically, these cells were positive only for vimentin on the mucinous lesion. On the circumference of the mucinous lesion, these cells expressed either CD34 or factor XIIIa (FXIIIa). Because vimentin was common to dermal mesenchymal cells, we defined the cells expressing CD34 or FXIIIa, except for vimentin+ cells lacking CD34 or FXIIIa, as dermal dendritic cells (DDC). The findings of the present case suggest that CD34+ or FXIIIa+ DDC and tryptase-positive mast cells on the perilesional area in combination with vimentin+ cells on the mucinous lesion might have given rise to the dermal deposition of mucin in our case. These cells, which are possibly activated in an autoimmune manner associated with rheumatoid arthritis, might play important roles in the development of dermal deposition of mucin in SHPM.     

Expression of CD1a and CD86 on scleroderma Langerhans cells

Scleroderma is a chronic autoimmune connective tissue disorder of unknown etiology that affects the microvasculature and loose connective tissue. Langerhans cells play an important role in the immune system of the skin. By immunohistochemistry we investigated the phenotypical characteristics of epidermal and dermal Langerhans cells and their spatial relationship with infiltrating lymphocytes in systemic scleroderma (SSc) and localized scleroderma. Skin samples were obtained from patients by 6 mm punch biopsy. Samples were stained with antibodies against CD1a and CD86. The number of cells stained with both antibodies in the dermal and epidermal infiltration was calculated. In contrast to normal skin, both types of scleroderma skin showed a marked increase in CD1a+ dermal Langerhans cells, whereas the number of CD1a+ cells in localized scleroderma was much higher than that in SSc (p < 0.05) either in the dermis or in the epidermis. The expression of CD86 was increased in the dermis of localized scleroderma compared with that in SSc or normal skin (p < 0.05). This study revealed that Langerhans cells may play an important role in the pathogenesis of scleroderma, especially in localized scleroderma. CD86 is predominantly expressed on dermal Langerhans cells in the lesional skin of localized scleroderma. Therefore, it might play an important role in the pathogenesis of localized scleroderma.     

Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides

Background It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders. Objectives In this study, we immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs in the lesional skin of psoriasis vulgaris, mycosis fungoides and eczematous dermatitis. Methods We used immunohistochemistry to examine the presence of Foxp3+ Tregs in fixed sections of the lesional skin from 16 patients with psoriasis vulgaris, 17 patients with mycosis fungides and 18 patients with eczematous dermatitis in addition to 10 normal skin samples. Results In normal skin, epidermal and dermal Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and eczematous dermatitis samples contained substantial numbers of epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+ cells was significantly lower in eczematous dermatitis than in psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+ cells was significantly lower in psoriasis vulgaris than in eczematous dermatitis or mycosis fungoides. Conclusions The lower percentage of epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis vulgaris, respectively, might contribute to their pathogenesis.     

iC3b arrests monocytic cell differentiation into CD1c-expressing dendritic cell precursors: a mechanism for transiently decreased dendritic cells in vivo after human skin injury by ultraviolet B

Our previous data indicated that C3, its bioactive product iC3b, and the iC3b ligand CD11b are critical for ultraviolet-induced immunosuppression. We thus hypothesized that iC3b is an important skin-based factor regulating CD11b+ monocytic cell function in the acute post-ultraviolet period. Although monocytic cell migration peaked at 1-3 d after ultraviolet exposure of skin, dermal CD1c dendritic cells underwent a rapid and prolonged depletion that did not recover until day 7. Because ultraviolet-induced iC3b deposits are reciprocally maximal on day 3, but fade by day 7, we next hypothesized that iC3b can be responsible for the delay in differentiation into dendritic cells of monocytic cells migrating into ultraviolet-exposed skin. Analysis of dermal cells derived from keratome biopsies suggested that iC3b exposure could inhibit the development of CD1c+ dermal cells. To model newly immigrating blood monocytes entering ultraviolet-exposed, iC3b-containing dermis, purified monocytes from human blood were induced with granulocyte-macrophage colony stimulating factor to generate a population of dendritic cell precursors expressing CD1c. Incubation with iC3b markedly inhibited the appearance of CD1c+ cells (p<0.05) and induced CD1c-CD14+ cells. This inhibition was reversed by coincubation with an anti-CD11b antibody that blocks the iC3b binding site. Other functions associated with dendritic cell maturation were also inhibited by iC3b, such as interleukin-12p70 production as well as CD80 and CD40 expression. Restimulation of monocytes for DC maturation revealed that iC3b induced a temporary inhibition of DC differentiation. Thus, a human skin response in which iC3b is transiently (3-7 d) generated in dermis, such as ultraviolet, can arrest monocytic skin-infiltrating cells from undergoing dendritic cell precursor differentiation.     

CD70-CD27 interaction augments CD8+ T-cell activation by human epidermal Langerhans cells

Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4+ T-cell and humoral immune responses; however, differences in the regulation of memory CD8+ T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8+ cells. Although tumor necrosis factor-α-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8+ cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+ T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8+ activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer.     

Comparison of the distribution and numbers of antigen-presenting cells among T-lymphocyte-mediated dermatoses: CD1a+, factor XIIIa+, and CD68+ cells in eczematous dermatitis,psoriasis, lichen planus and graft-versus-host disease

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a(+) dendritic cells (DCs), factor XIIIa(+) dermal DCs, and CD68(+) macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a(+) cells and factor XIIIa(+) cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa(+) cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a(+) cells. Interestingly, factor XIIIa(+) cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a(+) cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases.     

Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells

CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.     

巨噬细胞是正常成人真皮中主要的细胞成分

目的 研究正常人真皮内的巨噬细胞和树枝状细胞占所有有核细胞的比率。方法 正常人8例,每例均取面部、躯干、四肢近端、四肢远端、手掌和足跖6个部位皮肤,进行铺片和纵行与水平连续切片。CD68,CD36单克隆抗体和FXIIIa多克隆抗体染色。观察这些巨噬细胞胞占真皮中所有有核细胞的比例。结果 CD68阳性巨噬细胞占真皮浅层所有有核细胞总数的67.5±17.1%, FXIIIa阳性真皮树枝状细胞为35.2±14.5%,CD36阳性细胞为27.0±11.4%。结论 巨噬细胞不仅是正常成人真皮中的主要的免疫细胞,而且是真皮内皮肤免疫防御功能的主要细胞。在真皮内还有一定数量的抗原提呈细胞。     

Differential expression of factor XIIIa and CD34 in cutaneous mesenchymal tumors

The histogenetic relationship amongst various dendritic cells of the dermis which may express markers including factor XIIIa (FXIIIa) or CD34 remains unclear. In this study we utilized a sensitive indirect immunoperoxidase staining technique to identify CD34 and FXIIIa, as well the monocyte/macrophage markers KP-1 and MAC 387 expression in a variety of cutaneous dermal tumors of mesenchymal origin to see if differentia] expression of CD34 vs FXIIIa exists. Tumors studied included dermatofibroma (DF) (N = 10), keloid (N=9), atypical fibroxanthoma (AFX) (N = 3), and dermatofibrosarcoma protuberans (DFSP) (N = 7). DF were all composed of FXIIIa + spindle-shaped and stellate tumor cells (mean score = 4.9 or ≥ 75% FXIIIa +) as previously reported, but these cells rarely (< 10%) expressed CD34. Six of 7 DFSP were found to be > 75% CD34+ and FXIIIa negative, while one DFSP was negative for both CD34 and FXIIIa. In all DFSP, there were trapped FXIIIa+ cells which were distinct from the spindle-shaped tumor cells. AFX showed sparse populations of FXIIIa + cells in the stroma (mean score = 1.33 or 10–25% positive), which were distinct from the atypical giant cells characteristic of these tumors. Keloid similarly contained trapped FXIIIa+ cells (mean score = 0.44 or < 5% positive) that were distinct from the spindle-shaped fibroblasts of the tumor mass. Dendritic and spindle-shaped cells within these tumors were consistently both KP-1 and Mac-387 negative, while all lesions studied were characterized by scattered round, histiocytic cells which were KP-1 + and/or Mac-387 + irrespective of tumor cell type. We suggest that these tumors can be delineated by their relative degrees of FXIIIa and CD34 expression and that these neoplasms may be a useful link with which to study the relationship between CD34+ cells and dermal dendrocytes.     

蕈样肉芽肿与扁平苔藓、银屑病浸润细胞的免疫组化比较

目的 探讨免疫表型对蕈样肉芽肿与扁平苔藓、银屑病鉴别诊断的意义.方法 应用ABC免疫组化技术检测15例蕈样肉芽肿,17例银屑病和17例扁平苔藓,6例正常人皮肤的CD1a、CD4、CD8、ICAM-1、LFA-1、HLA-DR(树枝状细胞)、CD30和CD7的表达情况.结果 蕈样肉芽肿表皮CD1a,CD30,ICAM-1(单一核细胞P<0.001,树枝状细胞P<0.01)的阳性细胞密度明显高于扁平苔藓、银屑病、正常人皮肤.蕈样肉芽肿表皮CD4,CD8,HLA-DR的阳性细胞密度明显高于扁平苔藓.蕈样肉芽肿真皮中CD1a阳性细胞的线性密度(P<0.01),真皮内ICAM-1和LFA-1阳性细胞百分比亦较扁平苔藓增多(P<0.05).蕈样肉芽肿表皮CD7阳性细胞与扁平苔藓、银屑病比较差异无统计学意义.银屑病和扁平苔鲜真皮内CD7阳性细胞百分比高于蕈样肉芽肿和正常人皮肤.结论 蕈样肉芽肿和扁平苔藓、银屑病皮损CD1a、CD4、CD8、ICAM-1、LFA-1、HLA-DR、CD30和CD7免疫表型有差异,其结果可为探讨发病机制提供线索.     

Proliferative activity of CD8(+) T cells as an important clue to analyze T cell-mediated inflammatory dermatoses

Abstract To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. Received: 13 December 2000 / Revised: 24 April 2001 / Accepted: 11 July 2001     

模拟日光照射后皮肤CD1a、CD68阳性细胞变化的研究

目的 观察正常人皮肤经日光模拟器照射（solar-simulated ultraviolet radiation,ssUVR)后,朗格汉斯细胞（Langerhans cells, LC）和CD68阳性的巨噬细胞的变化。方法14名健康汉族女性志愿者于背部非曝光部位接受ssUVR照射。选择2个正方形部位,一处为正常对照,另一处为每日一次ssUVR照射。第4天照射后的72小时,进行活检取材。对所有标本进行CD1a和CD68免疫组化染色。结果 未照射部位正常表皮内的LC密度为258±61个/mm2,ssUVR照射部位的LC密度明显降低为96±53个/mm2,LC的形态不完整,树突变短而不明显。真皮浅层CD68阳性的巨噬细胞,未照射部位密度为290±22个/mm2,ssUVR照射部位的密度升高为399±65个/mm2。经过照射后真皮这些巨噬细胞数目明显增多位置上移,形态上树突变长并且大多数互相连接紧密。结论ssUVR照射可使LC数目减少,形态破损。真皮内的巨噬细胞则增高,这似有助于弥补紫外线照射对局部免疫的抑制作用。     

蕈样肉芽肿浸润性皮损中树突细胞表型特征的研究

目的 探讨蕈样肉芽肿(MF)皮损中树突细胞(DC)表型及其临床意义。方法 检测DC表面分子的单克隆抗体和免疫组化技术。结果 MF斑片／斑块期的表皮及真皮浅层内存在大量的未成熟DC和成熟DC，主要是CD1a^ 、CD1c^ 、Lag^ ／Langerin^ 未成熟DC和CD83^ DC-Lamp^ 成熟DC。肿瘤期的真皮内也见大量的CD1a^ 、CD1c^ 未成熟DC和CD83^ DC-Lamp^ 成熟DC，但Lag^ ／Langerin^ DC更多见于表皮和真皮浅层．真皮深层少见，而此处CD1a^ 、CD1c^ 未成熟DC明显增多。结论 在MF斑片／斑块期，表皮朗格汉斯细胞发生了迁移，可能参与了抗肿瘤免疫反应，而肿瘤期真皮内大量CD1a^ DC可能对相应的免疫耐受产生作用。     

Characterization of factor XIIIa+ dendritic cells in dermatofibroma: Immunohistochemical, electron and immunoelectron microscopical observations

BACKGROUND: Previous studies indicate that FXIIIa+ proliferative cells are the cells constituting DFs, however, in spite of the high incidence of DFs, there is a little information in the literature regarding ultrastructural characteristics of the FXIIIa+ dendritic cells on DFs. OBJECTIVES: In this study, we examined the fine structures and potential heterogeneity among the subgroup of factor XIIIa (FXIIIa) positive dendritic cells consisted of eleven cases of dermatofibroma (DF). METHODS: Immunohistochemical, electron microscopical, and immunoelectron microscopical techniques were utilized. RESULTS: We demonstrated (i) the immunohistochemical labeling of FXIIIa and CD68 in the DFs. The reactivity was stronger in histiocytic lesions than in fibroblastic lesions. On the other hand, the labeling of HHF35 was mainly in fibroblastic lesions. (ii) The fibroblastic and histiocytic cells on DFs displayed the same basic fine structures; moderate or abundant rough endoplasmic reticulum (RER), lipid droplets and/or bundles of myofilaments in varying proportions. Macular adherence connections between neighboring cells were common. (iii) They also showed the similar features to dermal dendritic cells (DDC), which have been well characterized with long cytoplasmic processes, abundant RER, fibronexus-like plaques and pinocytotic vesicles. (iv) FXIIIa expressions were found within the cytoplasm of both fibroblastic and histiocytic cells in association with the nucleus by immunoelectron microscopy. The labeling was stronger in the histiocytic cells and the cells expressing elongated cytoplasmic processes than in the fibroblastic cells. CONCLUSION: The FXIIIa+ dendritic cells might be an essential cell of DF, and might have potential to develop HHF35+ fibroblastic or CD68+ histiocytic cells, under appropriate stimuli. The FXIIIa+ dendritic cells might be originated from DDC.