Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage

Vermi, William; Lonardi, Silvia; Morassi, Mauro; Rossini, Claudia; Tardanico, Regina; Venturini, Marina; Sala, Raffaella; Tincani, Anǵela; Poliani, Pietro Luigi; Calzavara‐Pinton, Piergiacomo; Cerroni, Lorenzo; Santoro, Amerigo; Facchetti, Fabio

doi:10.1016/j.imbio.2009.06.013

Cited by 131 publications

(143 citation statements)

References 51 publications

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“…The same procedure was used for cytological and cell-block samples; the former were represented by slides previously stained with papanicolaou or hematoxylin-eosin, as previously described. 59 On selected cases, especially to distinguish between mesothelial cells and associated histiocytes, double immunohistochemistry for BAP1 combined either with epithelial membrane antigen (Leica Microsystem), calretinin (Invitrogen, Carlsbad, CA, USA), or cytokeratin 5/6 (Invitrogen) as mesothelial markers and CD11c (Leica Microsystems) and CD68 (clone PGM1, Dako, Glostrup, Denmark) as histiocyte markers was performed, as previously described, 60 using the Mach 4-alkaline phosphatase (AP) detection system (Biocare Medical, Concord, CA, USA) and Ferangi Blue (Biocare Medical) or New Fucsin (Dako) as chromogens.…”

Section: Bap1 Immunohistochemistrymentioning

confidence: 99%

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

et al. 2015

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The distinction between malignant mesothelioma and reactive mesothelial proliferation can be challenging both on histology and cytology. Recently, variants of the BRCA1-associated protein 1 (BAP1) gene resulting in nuclear protein loss were reported in hereditary and sporadic mesothelioma. Using immunohistochemistry, we evaluated the utility of BAP1 expression in the differential diagnosis between mesothelioma and other mesothelial proliferations on a large series of biopsies that included 212 mesotheliomas, 12 benign mesothelial tumors, and 42 reactive mesothelial proliferations. BAP1 stain was also performed in 70 cytological samples (45 mesotheliomas and 25 reactive mesothelial proliferations). BAP1 was expressed in all benign mesothelial tumors, whereas 139/212 (66%) mesotheliomas were BAP1 negative, especially in epithelioid/biphasic compared with sarcomatoid/desmoplastic subtypes (69% vs 15%). BAP1 loss was homogeneous in neoplastic cells except for two epithelioid mesotheliomas showing tumor heterogeneity. By fluorescence in situ hybridization, BAP1 protein loss was paralleled by homozygous deletion of the BAP1 locus in the vast majority of BAP1-negative tumors (31/41, 76%), whereas 9/10 BAP1-positive mesotheliomas were normal. In biopsies interpreted as reactive mesothelial proliferation BAP1 loss was 100% predictive of malignancy, as all 6 cases subsequently developed BAP1-negative mesothelioma, whereas only 3/36 (8%) BAP1-positive cases progressed to mesothelioma. On cytology/cell blocks, benign mesothelial cells were invariably positive for BAP1, whereas 64% of mesotheliomas showed loss of protein; all 6 cases showing BAP1 negativity were associated with histological diagnosis of BAP1-negative mesothelioma. BAP1 stain also showed utility in the differential of mesothelioma from most common pleural and peritoneal mimickers, such as lung and ovary carcinomas, with specificity and sensitivity of 99/70% and 100/70%, respectively. Our results show that BAP1 protein is frequently lost in mesothelioma, especially of epithelioid/biphasic subtype and is commonly associated with homozygous BAP1 deletion. BAP1 immunostain represents an excellent biomarker with an unprecedented specificity (100%) in the distinction between benign and malignant mesothelial proliferations. Finding BAP1 loss in mesothelial cells should prompt to immediately reevaluate the patient; moreover, it might be useful in mapping tumor extent and planning surgical resection.

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Section: Bap1 Immunohistochemistrymentioning

confidence: 99%

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

et al. 2015

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“…Conversely, in other skin diseases, such as atopic dermatitis, PDCs are not recruited to the inflamed tissue [53]. In LE and psoriasis, cutaneous accumulation of PDCs is associated with the local activation of the chemerin/ChemR23 axis (Box 1) [55,57,63]. In particular, chemerin is strongly induced in keratinocytes, dermal vessels and fibroblasts, whereas skin infiltrating PDCs strongly express ChemR23.…”

Section: Reviewmentioning

confidence: 99%

“…In psoriasis, PDCs infiltration is restricted largely to the dermis, and predominantly found in early phases of the disease [57,62]. In contrast, in LE skin lesions PDCs persist during the entire spectrum of the disease [63] and are located, not only in the dermis, but also at the dermo-epidermal junction in areas of epithelial cell damage. These findings suggest a novel view of the role of these cells in skin autoimmunity, where PDCs might coordinate the dermal immune reaction and sustain epithelial damage via secretion of cytotoxic molecules.…”

Section: Reviewmentioning

confidence: 99%

Trafficking properties of plasmacytoid dendritic cells in health and disease

Sozzani

Vermi

Prete

et al. 2010

Trends in Immunology

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“…14,19,20 Moreover, pDC leukemia/lymphoma is often associated with isolated cutaneous lesions because of skin accumulation of leukemic pDCs. 21 Inducible CXCR3 ligands (CXCL9/10/11) and chemerin, expressed on inflamed endothelium, have been reported to direct pDC extravasation to peripheral inflamed tissues.…”

Section: Introductionmentioning

confidence: 99%

CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues

Sisirak

Vey

Vanbervliet

et al. 2011

Blood

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Absent in peripheral tissues during homeostasis, human plasmacytoid dendritic cells (pDCs) are described in inflamed skin or mucosa. Here, we report that, unlike blood pDCs, a subset of tonsil pDCs express functional CCR6 and CCR10, and their respective ligands CCL20 and CCL27are detected in inflamed epithelia contacting blood dendritic cell antigen 2 ؉ pDCs. Moreover, pDCs are recruited to imiquimod-treated skin tumors in WT but not CCR6-deficient mice, and competitive adoptive transfers reveal that CCR6-deficient pDCs are impaired in homing to inflamed skin tumors after intravenous transfer. On IL-3 culture, CCR6 and CCR10 expression is induced on human blood pDCs that become responsive to CCL20 and CCL27/ CCL28, respectively. Interestingly, unlike myeloid DC, blood pDCs initially upregulate CCR7 expression and CCL19 responsiveness on IL-3 ؎ CpG-B and then acquire functional CCR6 and CCR10. Finally, IL-3-differentiated CCR6 ؉ CCR10 ؉ pDCs secrete high levels of IFN-␣ in response to virus. Overall, we propose an unexpected pDCs migratory model that may best apply for mucosal-associated lymphoid tissues. After CCR7-mediated extravasation into lymphoid tissues draining inflamed epithelia, blood pDCs may be instructed to up-regulate CCR6 and/or CCR10 allowing their homing into inflamed epithelia (in mucosae or skin IntroductionPlasmacytoid dendritic cells (pDCs) play an important role in innate antiviral immunity by rapidly secreting abundant type I IFNs after exposure to various RNA or DNA viruses. 1 This unique ability is mediated through their selective expression of TLR7 and TLR9, 2 involved in pathogen sensing. After activation, pDCs differentiate into a distinct type of mature DCs directing T-cell responses with high flexibility. 1 Thus, pDCs play a critical role at the interface between innate and adaptive immunity.pDCs are commonly detected in peripheral blood and lymphoid organs. 1 Unlike myeloid DC (mDCs), they are absent from peripheral epithelial tissues under steady-state conditions, fail to migrate in response to inflammatory chemokines in vitro, and are constitutively recruited from the blood to the lymph nodes through high endothelial venule, a process involving CD62L, CCR7, ChemR23, and CXCR3/4. 3-10 On maturation, both DC subsets up-regulate CCR7 expression and respond to the lymph nodehoming chemokines CCL19 and CCL21, 5,7,8 allowing their recruitment in T-cell areas where they initiate adaptive immune responses. It was recently shown in mice that CCR7 plays an essential role for the homing of pDCs, regardless of their activation status, to lymph node under both steady-state and inflammatory conditions. 10However, pDCs also accumulate in inflamed epithelial tissues during noninfectious and infectious disorders 9,11-18 and participate in inflammatory chronic diseases, such as psoriasis and systemic lupus erythematosus. 14,19,20 Moreover, pDC leukemia/lymphoma is often associated with isolated cutaneous lesions because of skin accumulation of leukemic pDCs. 21 Inducible CXCR3 ligands (CXCL9/10/11...

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Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage

Cited by 131 publications

References 51 publications

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

Trafficking properties of plasmacytoid dendritic cells in health and disease

CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues

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