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

Abstract Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tiss...

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Veröffentlicht in:Immunobiology (1979) 2009-09, Vol.214 (9), p.877-886
Hauptverfasser: Vermi, William, Lonardi, Silvia, Morassi, Mauro, Rossini, Cristina, Tardanico, Regina, Venturini, Marina, Sala, Raffaella, Tincani, Angela, Poliani, Pietro Luigi, Calzavara-Pinton, Pier Giacomo, Cerroni, Lorenzo, Santoro, Amerigo, Facchetti, Fabio
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container_end_page 886
container_issue 9
container_start_page 877
container_title Immunobiology (1979)
container_volume 214
creator Vermi, William
Lonardi, Silvia
Morassi, Mauro
Rossini, Cristina
Tardanico, Regina
Venturini, Marina
Sala, Raffaella
Tincani, Angela
Poliani, Pietro Luigi
Calzavara-Pinton, Pier Giacomo
Cerroni, Lorenzo
Santoro, Amerigo
Facchetti, Fabio
description Abstract Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate ( r =0.40; p
doi_str_mv 10.1016/j.imbio.2009.06.013
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Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate ( r =0.40; p &lt;0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B. This study confirms cutaneous PDC infiltration as hallmark of LE. 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Selective tropism at the site of epithelial apoptotic damage</title><title>Immunobiology (1979)</title><addtitle>Immunobiology</addtitle><description>Abstract Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate ( r =0.40; p &lt;0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B. This study confirms cutaneous PDC infiltration as hallmark of LE. 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Selective tropism at the site of epithelial apoptotic damage</atitle><jtitle>Immunobiology (1979)</jtitle><addtitle>Immunobiology</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>214</volume><issue>9</issue><spage>877</spage><epage>886</epage><pages>877-886</pages><issn>0171-2985</issn><eissn>1878-3279</eissn><abstract>Abstract Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate ( r =0.40; p &lt;0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B. This study confirms cutaneous PDC infiltration as hallmark of LE. The topographical segregation in D-PDC and J-PDC suggests a novel view of the role of these cells in skin autoimmunity.</abstract><cop>Netherlands</cop><pub>Elsevier GmbH</pub><pmid>19625100</pmid><doi>10.1016/j.imbio.2009.06.013</doi><tpages>10</tpages></addata></record>
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subjects Advanced Basic Science
Allergy and Immunology
Apoptosis
Cell Movement
Chimerin Proteins - metabolism
Cutaneous
Dendritic Cells - immunology
Dermis - immunology
Dermis - pathology
Humans
Immunohistochemistry
Interferon
Interferon Type I - biosynthesis
Kidney - immunology
Kidney - pathology
Lupus erythematosus
Lupus Erythematosus, Cutaneous - immunology
Lupus Erythematosus, Cutaneous - pathology
Lysosomal Membrane Proteins - metabolism
Neoplasm Proteins - metabolism
Plasmacytoid dendritic cell
Skin - immunology
Skin - pathology
T-Box Domain Proteins - metabolism
title Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage
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