Poposki J A, Peterson S, Welch K, Schleimer R P, Hulse K E, Peters A T, Norton J, Suh L A, Carter R, Harris K E, Grammer L C, Tan B K, Chandra R K, Conley D B, Kern R C, Kato A
Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Clin Exp Allergy. 2015 Feb;45(2):384-93. doi: 10.1111/cea.12471.
Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2 inflammation, the mechanism underlying the onset and amplification of this inflammation has not been fully elucidated. Dendritic cells (DCs) are major antigen-presenting cells, central inducers of adaptive immunity and critical regulators of many inflammatory diseases. However, the presence of DCs in CRS, especially in nasal polyps (NPs), has not been extensively studied.
The objective of this study was to characterize DC subsets in CRS.
We used real-time PCR to assess the expression of mRNA for markers of myeloid DCs (mDCs; CD1c), plasmacytoid DCs (pDCs; CD303) and Langerhans cells (LCs; CD1a, CD207) in uncinate tissue (UT) from controls and patients with CRS as well as in NP. We assayed the presence of DCs by immunohistochemistry and flow cytometry.
Compared to UT from control subjects (n = 15) and patients with CRS without NP (CRSsNP) (n = 16) and CRSwNP (n = 17), mRNAs for CD1a and CD1c were significantly elevated in NPs (n = 29). In contrast, CD207 mRNA was not elevated in NPs. Immunohistochemistry showed that CD1c(+) cells but not CD303(+) cells were significantly elevated in NPs compared to control subjects or patients with CRSsNP. Flow cytometric analysis showed that CD1a(+) cells in NPs might be a subset of mDC1s and that CD45(+) CD19(-) CD1c(+) CD11c(+) CD141(-) CD303(-) HLA-DR(+) mDC1s and CD45(+) CD19(-) CD11c(+) CD1c(-) CD141(high) HLA-DR(+) mDC2s were significantly elevated in NPs compared to UT from controls and CRSsNP, but CD45(+) CD11c(-) CD303(+) HLA-DR(+) pDCs were only elevated in NPs compared to control UT.
Myeloid DCs are elevated in CRSwNP, especially in NPs. Myeloid DCs thus may indirectly contribute to the inflammation observed in CRSwNP.
尽管伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)以Th2炎症为特征,但这种炎症的发生和放大机制尚未完全阐明。树突状细胞(DCs)是主要的抗原呈递细胞,是适应性免疫的主要诱导者和许多炎症性疾病的关键调节因子。然而,CRS中DCs的存在,尤其是在鼻息肉(NPs)中的存在,尚未得到广泛研究。
本研究的目的是对CRS中的DC亚群进行特征描述。
我们使用实时PCR评估来自对照组和CRS患者以及NP的钩突组织(UT)中髓样DCs(mDCs;CD1c)、浆细胞样DCs(pDCs;CD303)和朗格汉斯细胞(LCs;CD1a、CD207)标志物的mRNA表达。我们通过免疫组织化学和流式细胞术检测DCs的存在情况。
与对照组(n = 15)、无NP的CRS患者(CRSsNP)(n = 16)和CRSwNP患者(n = 17)的UT相比,NP(n = 29)中CD1a和CD1c的mRNA显著升高。相比之下,NP中CD207 mRNA未升高。免疫组织化学显示,与对照组或CRSsNP患者相比,NP中CD1c(+)细胞而非CD303(+)细胞显著升高。流式细胞术分析显示,NP中的CD1a(+)细胞可能是mDC1s的一个亚群,并且与对照组和CRSsNP的UT相比,NP中CD45(+) CD19(-) CD1c(+) CD11c(+) CD141(-) CD303(-) HLA-DR(+) mDC1s和CD45(+) CD19(-) CD11c(+) CD1c(-) CD141(高) HLA-DR(+) mDC2s显著升高,但与对照UT相比,只有NP中CD45(+) CD11c(-) CD303(+) HLA-DR(+) pDCs升高。
CRSwNP中髓样DCs升高,尤其是在NP中。因此,髓样DCs可能间接导致CRSwNP中观察到的炎症。