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
Department of Pathology, University of Brescia, Italy.
Immunobiology. 2009;214(9-10):877-86. doi: 10.1016/j.imbio.2009.06.013. Epub 2009 Jul 21.
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<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.
近期证据表明浆细胞样树突状细胞（pDC）通过产生I型干扰素在红斑狼疮（LE）发病机制中起重要作用。利用多种可特异性识别固定组织中pDC的试剂（CD123、BDCA2和CD2ap），我们调查了74例LE患者队列中pDC的出现情况。绝大多数LE活检标本（67/74；90.5%）显示有pDC的皮肤浸润。与系统性红斑狼疮（SLE）相比，pDC在皮肤型LE中更频繁出现（96.4%对72.2%）且数量更多，并且与炎症浸润密度相关（r = 0.40；p < 0.001）。SLE中pDC减少可能与该细胞群体更广泛的组织分布有关，在所研究的24例病例中有11例（45.8%）在肾脏中出现了pDC即表明了这一点。皮肤pDC的分布呈现两种不同模式。更常见的是，pDC出现在真皮血管周围炎性结节内，与CD208 + 成熟树突状细胞和T-bet + 细胞相关[D-pDC]。在严重上皮损伤区域，沿着真皮 - 上皮交界处观察到第二种成分[J-pDC]，与细胞毒性T细胞相关。值得注意的是，在64%的LE活检标本中，在内皮细胞和颗粒层角质形成细胞中观察到了chemerin反应性。LE中的皮肤pDC强烈产生I型干扰素，弥漫性MxA表达和细胞毒性分子颗粒酶B表明了这一点。本研究证实皮肤pDC浸润是LE的标志。D-pDC和J-pDC中的地形学分离提示了这些细胞在皮肤自身免疫中作用的新观点。
