Karouni Mirna, Kurban Mazen, Abbas Ossama
Dermatology Department, American University of Beirut Medical Center, Riad El Solh St, P.O.Box 11-0236, Beirut, Lebanon.
Arch Dermatol Res. 2016 Sep;308(7):487-92. doi: 10.1007/s00403-016-1671-6. Epub 2016 Jul 2.
Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.
浆细胞样树突状细胞(pDC)是I型干扰素(IFN)的最强有力生产者,这使它们能够提供抗病毒抵抗力,并通过控制髓样树突状细胞、淋巴细胞和自然杀伤细胞的功能来连接先天免疫和适应性免疫。pDC参与多种感染性疾病(尤其是病毒性疾病,如传染性软疣(MC))、炎症/自身免疫性疾病和肿瘤性疾病的发病机制。卡波西肉瘤(KS)是一种多灶性、系统性淋巴血管增生性肿瘤,与卡波西肉瘤相关疱疹病毒(KSHV)感染有关。显微镜检查通常除了血管变化和梭形细胞增殖外,还表现为慢性炎症性淋巴细胞浆细胞浸润。尽管对KSHV所采用的免疫逃逸策略进行了广泛研究,但pDC在KS中的作用却很少被研究。鉴于此,我们打算研究KS皮肤病变中pDC的出现情况和活性。对20例经典KS进行了BDCA-2(特异性pDC标志物)和MxA(局部I型IFN产生的替代标志物)的免疫组织化学染色,对照组为20例炎症性MC。正如预期的那样,在所有炎症性MC病例(20例中的20例,100%)中,BDCA-2+ pDC大量存在,MxA呈弥漫性强烈表达(表明局部I型IFN产生)。虽然在所有KS病例中都有pDC,但KS中的pDC数量明显少于炎症性MC病例,并且在大多数KS病例中MxA表达呈斑片状/弱阳性。总之,pDC是KS中炎症宿主反应的一部分;然而,它们的数量通常较少,I型IFN产生减少,这可能与KSHV通过产生能够抑制IFN产生以及pDC功能的不同病毒蛋白来逃避免疫系统的能力有关。