原標(biāo)題：高維分析確定了多細(xì)胞因子T細(xì)胞亞群，并支持IL-21在特應(yīng)性皮炎中的作用
背景：流式細(xì)胞術(shù)是一種廣為接受的免疫分析方法；然而，它的價(jià)值受限于可以同時(shí)分析的標(biāo)記物的數(shù)量。質(zhì)譜流式細(xì)胞術(shù)/CyTOF提供大規(guī)模免疫表征整合成大量參數(shù)。雖然在特應(yīng)性皮炎(AD)中報(bào)告了部分血液表型，但對(duì)利用新的靶向治療至關(guān)重要的患者綜合分析尚不可用。IL-21可能與炎癥性皮膚病有關(guān)，但其在AD中的作用尚未確定。
方法：我們研究了20名中度至重度AD和15名對(duì)照者血液中的T細(xì)胞極化。使用CyTOF和無(wú)監(jiān)督分析，我們測(cè)量了活化的極性CD4+/CD8+ T細(xì)胞亞群頻率和平均金屬?gòu)?qiáng)度。使用免疫組織化學(xué)、免疫熒光和qRT-PCR分析皮膚樣本。
結(jié)果：通過(guò)檢查24個(gè)表面、細(xì)胞內(nèi)標(biāo)記和轉(zhuǎn)錄因子，我們確定了6個(gè)CD4+和5個(gè) CD8+ T 細(xì)胞元簇。與對(duì)照組相比，AD中CD4+皮膚歸巢IL-13+單細(xì)胞因子和新型IL-13+IL-21+多細(xì)胞因子元簇增加（p < .01）。雖然 IL-13 特征表征了兩個(gè)簇，但 IL-21+ 組的水平顯著更高。兩個(gè)集群都與AD嚴(yán)重程度相關(guān)（r = 0.49，p = .029）。手動(dòng)門(mén)控證實(shí)了這些結(jié)果并確定了AD中的其他多細(xì)胞因子亞群。通過(guò)mRNA表達(dá)驗(yàn)證的免疫組織化學(xué)和免疫熒光顯示，IL-21計(jì)數(shù)顯著增加，并且與AD皮膚中的IL-13/IL-4R共定位。
結(jié)論：多細(xì)胞因子特征是中重度AD的特征，這可能解釋了對(duì)一種細(xì)胞因子靶向的部分治療反應(yīng)，尤其是在重度患者中。血液和皮膚中顯著的IL-21特征暗示了IL-21在AD中的潛在致病作用。


延伸閱讀
Allergy                                                
High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis
DOI: 10.1111/all.14845
Abstract:
Background: Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients’ comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL-21 may be involved in inflammatory skin diseases but its role in AD is not well established.
Methods: We studied T-cell polarization in the blood of 20 moderate-to-severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4+/CD8+ T-cell subsets. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to analyze skin samples.
Results: Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4+ and five CD8+ T-cell metaclusters. A CD4+ skin-homing IL-13+monocytokine and a novel IL-13+IL-21+ multicytokine metaclusters were increased in AD vs. controls (p < .01). While IL-13 signature characterized both clusters, levels were significantly higher in the IL-21+ group. Both clusters correlated with AD severity (r = 0.49, p = .029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL-21 counts and colocalization with IL-13/IL-4R in AD skin.
Conclusion: A multicytokine signature characterizes moderate-to-severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL-21 signature in blood and skin hints for a potential pathogenic role of IL-21 in AD.
First Author:
Tali Czarnowicki
Correspondence:
Emma Guttman-Yassky, The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1047, New York, NY 10029-6574, USA.
2021-10-27 Article 
　　創(chuàng)建過(guò)敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過(guò)敏患者提供專(zhuān)業(yè)診斷、治療、預(yù)防的共享平臺(tái)。