免疫模块指导炎症性皮肤病的诊断和个性化治疗-动脉网

Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases

Nature 等信源发布 2024-12-18 20:15



可切换为仅中文







AbstractPrevious advances have identified immune pathways associated with inflammatory skin diseases, leading to the development of targeted therapies. However, there is a lack of molecular approaches that delineate these pathways at the individual patient level for personalized diagnostic and therapeutic guidance.

摘要先前的进展已经确定了与炎症性皮肤病相关的免疫途径，从而导致了靶向治疗的发展。然而，缺乏在个体患者水平上描述这些途径的分子方法，以进行个性化诊断和治疗指导。

Here, we conduct a cross-comparison of expression profiles from multiple inflammatory skin diseases to identify gene modules defining relevant immune pathways. Seven modules are identified, representing key immune pathways: Th17, Th2, Th1, Type I IFNs, neutrophilic, macrophagic, and eosinophilic. These modules allow the development of a molecular map with high diagnostic efficacy for inflammatory skin diseases and clinico-pathologically undetermined cases.

在这里，我们对来自多种炎症性皮肤病的表达谱进行交叉比较，以鉴定定义相关免疫途径的基因模块。确定了七个模块，代表关键的免疫途径：Th17，Th2，Th1，I型IFN，嗜中性粒细胞，巨噬细胞和嗜酸性粒细胞。这些模块允许开发对炎症性皮肤病和临床病理学未确定病例具有高诊断功效的分子图谱。

Aligning dominant modules with treatment targets offers a rational framework for treatment selection, improving response rates in both treatment-naïve patients and non-responders to targeted therapies. Overall, our approach offers precision medicine for inflammatory skin diseases, utilizing transcriptional modules to support diagnosis and guide personalized treatment selection..

将主要模块与治疗目标相结合，为治疗选择提供了一个合理的框架，提高了未接受治疗的患者和无反应者对靶向治疗的反应率。总体而言，我们的方法为炎症性皮肤病提供了精准医学，利用转录模块支持诊断并指导个性化治疗选择。。

IntroductionOver the last decade, dermatology has undergone a remarkable translational revolution marked by the emergence of numerous molecular-based therapies for inflammatory skin conditions. This transformative progress owes its success to a profound comprehension of immune pathways, encompassing both adaptive pathways linked to T helper (Th) cell differentiation Th1, Th21, Th172, T regulatory cells3 and innate pathways associated with the generation of type I IFNs4 and IL-1 cytokines5.

引言在过去的十年中，皮肤病学经历了一场显着的转化革命，其标志是出现了许多基于分子的炎症性皮肤病治疗方法。这种变革性进展的成功归功于对免疫途径的深刻理解，包括与T辅助（Th）细胞分化Th1，Th21，Th172，T调节细胞3相关的适应性途径以及与I型IFNs4和IL-1细胞因子产生相关的先天途径5。

These pathways are now established as integral to the pathogenesis of common inflammatory skin disorders, such as psoriasis, characterized by Th17 involvement6,7,8, atopic dermatitis (AD), characterized by Th2 involvement9,10,11, lichen planus (LP), characterized by Th1 involvement12, lupus erythematosus (LE), a type I IFN-related disorder13,14, and neutrophilic diseases, influenced by cytokines of the IL-1 family15.

这些途径现在被确定为常见炎症性皮肤病发病机制的组成部分，例如牛皮癣，其特征在于Th17参与6,7,8，特应性皮炎（AD），其特征在于Th2参与9,10,11，扁平苔藓（LP），其特征在于Th1参与12，红斑狼疮（LE），I型IFN相关疾病13,14和中性粒细胞疾病，受IL-1家族细胞因子的影响15。

Molecular-based therapies have emerged as effective means to target these pathways, including anti-IL23 and IL-17A/F monoclonal antibodies for Th17 inhibition in psoriasis16,17,18,19,20,21, anti-IL-4RA and anti-IL-13 monoclonal antibodies for Th2 blockade in AD22,23,24, JAK1/2 inhibitors for Th1 inhibition in LP12,25,26, anti-IFN-αβ receptor (IFNAR) monoclonal antibodies for type I IFN signalling blockage in LE27, and anti-IL-1R and anti-IL-36R to mitigate neutrophilic inflammation in neutrophilic diseases28,29,30,31,32,33.

基于分子的疗法已成为靶向这些途径的有效手段，包括用于银屑病Th17抑制的抗IL23和IL-17A/F单克隆抗体16,17,18,19,20,21，用于AD22,23,24中Th2阻断的抗IL-4RA和抗IL-13单克隆抗体，用于LP12,25,26中Th1抑制的JAK1/2抑制剂，用于LE27中I型IFN信号传导阻断的抗IFN-αβ受体（IFNAR）单克隆抗体，以及用于减轻中性粒细胞疾病中性粒细胞炎症的抗IL-1R和抗IL-36R 28,29,30,31,32,33。

Despite the substantial therapeutic efficacy of these molecular treatments, clinicians often encounter patients who do not respond, prompting questions about the accuracy of diagnosis, appropriateness of the chosen therapeutic target, or the possibility of an immune shift under immune pathway blockade.Presently, a notable gap exists in molecular approa.

尽管这些分子治疗具有显着的治疗效果，但临床医生经常遇到没有反应的患者，这引发了关于诊断准确性，所选治疗靶标的适当性或免疫途径阻断下免疫转移的可能性的问题。目前，分子方法存在显着差距。

Data availability

数据可用性

Nanostring transcriptomics datasets generated for this publication and re-analyzed from Di Domizio J. et al.36 are deposited at GEO data repository under the accession number GSE280220 and GSE193068 respectively. All other data are available in the article and its Supplementary files or from the corresponding author upon request. Source data are provided with this paper..

为本出版物生成并由Di Domizio J.等人重新分析的Nanostring转录组学数据集分别以登录号GSE280220和GSE193068保存在GEO数据库中。所有其他数据均可在文章及其补充文件中获得，或应要求从通讯作者处获得。本文提供了源数据。。

Code availability

代码可用性

The codes needed to reproduce analysis and findings of this study are available in the GitHub repository https://github.com/derchuv/persomed.

重现这项研究的分析和发现所需的代码可以在GitHub存储库中找到https://github.com/derchuv/persomed.

ReferencesMosmann, T. R. & Coffman, R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev. Immunol. 7, 145–173 (1989).Article

参考文献Mosmann，T.R。＆Coffman，R.L。TH1和TH2细胞：不同的淋巴因子分泌模式导致不同的功能特性。年度免疫修订版。7145-173（1989）。文章

PubMed

Google Scholar

谷歌学者

Korn, T., Bettelli, E., Oukka, M. & Kuchroo, V. K. IL-17 and Th17 Cells. Annu Rev. Immunol. 27, 485–517 (2009).Article

Korn，T.，Bettelli，E.，Oukka，M。＆Kuchroo，V.K。IL-17和Th17细胞。年度免疫修订版。27485-517（2009）。文章

PubMed

Google Scholar

谷歌学者

Sakaguchi, S. et al. Regulatory T Cells and Human Disease. Annu Rev. Immunol. 38, 541–566 (2020).Article

Sakaguchi，S.等人，《调节性T细胞与人类疾病》。年度免疫修订版。38541-566（2020）。文章

PubMed

Google Scholar

谷歌学者

Theofilopoulos, A. N., Baccala, R., Beutler, B. & Kono, D. H. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev. Immunol. 23, 307–336 (2005).Article

。年度免疫修订版。2307-336（2005）。文章

PubMed

Google Scholar

谷歌学者

Dinarello, C. A. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev. Immunol. 27, 519–550 (2009).Article

Dinarello，C.A。白细胞介素-1家族的免疫和炎症功能。年度免疫修订版。27519-550（2009）。文章

PubMed

Google Scholar

谷歌学者

Nestle, F. O., Kaplan, D. H. & Barker, J. Psoriasis. N. Engl. J. Med 361, 496–509 (2009).Article

Nestle，F.O.，Kaplan，D.H.和Barker，J.银屑病。N.安吉尔。J.与361496-509（2009）。文章

PubMed

Google Scholar

谷歌学者

Lowes, M. A., Suarez-Farinas, M. & Krueger, J. G. Immunology of psoriasis. Annu Rev. Immunol. 32, 227–255 (2014).Article

Lowes，M.A.，Suarez-Farinas，M。＆Krueger，J.G。牛皮癣免疫学。年度免疫修订版。32227-255（2014）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Griffiths, C. E. M., Armstrong, A. W., Gudjonsson, J. E. & Barker, J. Psoriasis. Lancet 397, 1301–1315 (2021).Article

Griffiths，C.E.M.，Armstrong，A.W.，Gudjonsson，J.E.和Barker，J.银屑病。《柳叶刀》3971301–1315（2021）。文章

PubMed

Google Scholar

谷歌学者

Bieber, T. Atopic dermatitis. N. Engl. J. Med 358, 1483–1494 (2008).Article

比伯，T.特应性皮炎。N.Engl。《医学杂志》3581483-1494（2008）。文章

PubMed

Google Scholar

谷歌学者

Brunner, P. M., Guttman-Yassky, E. & Leung, D. Y. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J. Allergy Clin. Immunol. 139, S65–S76 (2017).Article

Brunner，P.M.，Guttman-Yassky，E.＆Leung，D.Y。特应性皮炎的免疫学及其与广谱和靶向治疗的可逆性。J、过敏临床。免疫。139，S65–S76（2017）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018).Article

Weidinger，S.，Beck，L.A.，Bieber，T.，Kabashima，K。＆Irvine，A.D。特应性皮炎。自然版本Dis。一本正经。4,1（2018）。文章

PubMed

Google Scholar

谷歌学者

Shao, S. et al. IFN-gamma enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus. Sci. Transl. Med. 11, eaav7561 (2019).Caielli, S., Wan, Z. & Pascual, V. Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond. Annu Rev. Immunol. 41, 533–560 (2023).Article .

Shao，S。等人。IFN-γ通过扁平苔藓中的JAK2/STAT1增强细胞介导的对角质形成细胞的细胞毒性。科学。翻译。。Caielli，S.，Wan，Z。＆Pascual，V。系统性红斑狼疮发病机制：干扰素及其后。年度免疫修订版。41533-560（2023）。文章。

PubMed

Google Scholar

谷歌学者

Wallace, D. J. Progress toward Better Treatment of Lupus. N. Engl. J. Med 387, 939–940 (2022).Article

Wallace，D.J。狼疮更好治疗的进展。N、英语。J、 Med 387939–940（2022）。文章

PubMed

Google Scholar

谷歌学者

Satoh, T. K., Mellett, M., Contassot, E. & French, L. E. Are neutrophilic dermatoses autoinflammatory disorders? Br. J. Dermatol 178, 603–613 (2018).Article

Satoh，T.K.，Mellett，M.，Contassot，E.＆French，L.E.是中性粒细胞性皮肤病自身炎症性疾病吗？Br.J.Dermatol 178603–613（2018）。文章

PubMed

Google Scholar

谷歌学者

Papp, K. A. et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. N. Engl. J. Med 376, 1551–1560 (2017).Article

Papp，K.A。等人，Risankizumab与Ustekinumab治疗中度至重度斑块状银屑病。N、英语。J、 Med 3761551-1560（2017）。文章

PubMed

Google Scholar

谷歌学者

Reich, K. et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet 390, 276–288 (2017).Article

Reich，K。等人。替拉基珠单抗与安慰剂或依那西普治疗慢性斑块型银屑病（reSURFACE 1和reSURFACE 2）：两项随机对照3期试验的结果。柳叶刀390276-288（2017）。文章

PubMed

Google Scholar

谷歌学者

Reich, K. et al. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. Lancet 394, 831–839 (2019).Article

Reich，K。等人。Guselkumab与secukinumab治疗中重度银屑病（ECLIPSE）：来自3期随机对照试验的结果。柳叶刀394831-839（2019）。文章

PubMed

Google Scholar

谷歌学者

Langley, R. G. et al. Secukinumab in plaque psoriasis-results of two phase 3 trials. N. Engl. J. Med 371, 326–338 (2014).Article

Langley，R.G.等人。Secukinumab治疗斑块状银屑病的两项3期临床试验结果。N、英语。J、 Med 371326-338（2014）。文章

PubMed

Google Scholar

谷歌学者

Gordon, K. B., Colombel, J. F. & Hardin, D. S. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N. Engl. J. Med 375, 2102 (2016).Article

Gordon，K.B.，Colombel，J.F。＆Hardin，D.S。Ixekizumab治疗中重度斑块状银屑病的3期临床试验。N、英语。J、 Med 3752102（2016）。文章

PubMed

Google Scholar

谷歌学者

Gordon, K. B. et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet 397, 475–486 (2021).Article

Gordon，K.B.等人，《Bimekizumab治疗中重度斑块状银屑病的疗效和安全性（BE READY）：一项多中心、双盲、安慰剂对照、随机戒断3期试验》。柳叶刀397475-486（2021）。文章

PubMed

Google Scholar

谷歌学者

Simpson, E. L. et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N. Engl. J. Med 375, 2335–2348 (2016).Article

Simpson，E.L.等人。Dupilumab与安慰剂治疗特应性皮炎的两项3期试验。N.Engl。《医学杂志》3752335-2348（2016）。文章

PubMed

Google Scholar

谷歌学者

Wollenberg, A. et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Dermatol 184, 437–449 (2021).Article

。Br.J.Dermatol 184437-449（2021）。文章

PubMed

Google Scholar

谷歌学者

Silverberg, J. I. et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N. Engl. J. Med 388, 1080–1091 (2023).Article

Silverberg，J.I.等人。Lebrikizumab治疗中度至重度特应性皮炎的两项3期临床试验。N、英语。J、 Med 3881080–1091（2023）。文章

PubMed

Google Scholar

谷歌学者

Damsky, W. et al. Treatment of severe lichen planus with the JAK inhibitor tofacitinib. J. Allergy Clin. Immunol. 145, 1708–1710 e1702 (2020).Article

Damsky，W。等人。用JAK抑制剂托法替尼治疗严重扁平苔藓。J、过敏临床。免疫。1451708–1710 e1702（2020）。文章

PubMed

Google Scholar

谷歌学者

Boll, S. L., Zahn, C. A. & Schlapbach, C. Rapid and sustained improvement of cutaneous lichen planus with oral JAK1 inhibitors. J. Eur. Acad. Dermatol Venereol. 38, e82–e85 (2024).Article

Boll，S.L.，Zahn，C.A。＆Schlapbach，C。口服JAK1抑制剂快速持续改善皮肤扁平苔藓。J、欧元Acad。皮肤性病。38，e82-e85（2024）。文章

PubMed

Google Scholar

谷歌学者

Morand, E. F. et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N. Engl. J. Med 382, 211–221 (2020).Article

Morand，E.F.等人，阿尼单抗治疗活动性系统性红斑狼疮的试验。N、英语。J、 Med 382211-221（2020）。文章

PubMed

Google Scholar

谷歌学者

Brenner, M., Ruzicka, T., Plewig, G., Thomas, P. & Herzer, P. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br. J. Dermatol 161, 1199–1201 (2009).Article .

Brenner，M.，Ruzicka，T.，Plewig，G.，Thomas，P。＆Herzer，P。用重组人白细胞介素-1受体拮抗剂anakinra靶向治疗PAPA（化脓性关节炎，坏疽性脓皮病和痤疮）综合征中的坏疽性脓皮病。Br.J.Dermatol 1611199-1201（2009）。文章。

PubMed

Google Scholar

谷歌学者

Delluc, A. et al. Efficacy of anakinra, an IL1 receptor antagonist, in refractory Sweet syndrome. Ann. Rheum. Dis. 67, 278–279 (2008).Article

Delluc，A。等人。IL1受体拮抗剂anakinra在难治性Sweet综合征中的疗效。安。瑞姆。Dis。67278-279（2008）。文章

PubMed

Google Scholar

谷歌学者

Tzanetakou, V. et al. Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa: A Randomized Clinical Trial. JAMA Dermatol 152, 52–59 (2016).Article

Tzanetakou，V。等人。Anakinra治疗严重化脓性汗腺炎的安全性和有效性：一项随机临床试验。JAMA Dermatol 152,52-59（2016）。文章

PubMed

Google Scholar

谷歌学者

Bachelez, H. et al. Trial of Spesolimab for Generalized Pustular Psoriasis. N. Engl. J. Med 385, 2431–2440 (2021).Article

Bachelez，H.等人，Spesolimab治疗泛发性脓疱性银屑病的试验。N、英语。J、医学3852431-2440（2021）。文章

PubMed

Google Scholar

谷歌学者

Guenin, S. H., Khattri, S. & Lebwohl, M. G. Spesolimab use in treatment of pyoderma gangrenosum. JAAD Case Rep. 34, 18–22 (2023).Article

Guenin，S.H.，Khattri，S。＆Lebwohl，M.G。Spesolimab用于治疗坏疽性脓皮病。JAAD Case Rep.34，18-22（2023）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Alavi, A. Spesolimab for Hidradenitis Suppurativa: A Proof-of-Concept Study. SKIN J. Cutan. Med. 7, s286 (2023).Article

Alavi，A。Spesolimab治疗化脓性汗腺炎：概念验证研究。皮肤J.Cutan。医学杂志7，s286（2023）。文章

Google Scholar

谷歌学者

Inkeles, M. S. et al. Comparison of molecular signatures from multiple skin diseases identifies mechanisms of immunopathogenesis. J. Invest Dermatol 135, 151–159 (2015).Article

Inkeles，M.S.等人。多种皮肤病分子特征的比较确定了免疫发病机制。J、 Invest Dermatol 135151–159（2015）。文章

PubMed

Google Scholar

谷歌学者

Aevermann, B. D. et al. Cross-Comparison of Inflammatory Skin Disease Transcriptomics Identifies PTEN as a Pathogenic Disease Classifier in Cutaneous Lupus Erythematosus. J. Invest Dermatol 144, 252–262.e254 (2024).Article

Aevermann，B.D.等人，《炎症性皮肤病转录组学的交叉比较》将PTEN鉴定为皮肤红斑狼疮的致病性疾病分类器。J、 Invest Dermatol 144252–262.e254（2024）。文章

PubMed

Google Scholar

谷歌学者

Domizio, J. D. et al. The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature 603, 145–151 (2022).Article

Domizio，J.D。等人。cGAS-STING途径驱动COVID-19中的I型IFN免疫病理学。自然603145-151（2022）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Collins, F. S. & Varmus, H. A new initiative on precision medicine. N. Engl. J. Med 372, 793–795 (2015).Article

Collins，F.S。和Varmus，H。精准医学的新倡议。N、英语。J、 Med 372793-795（2015）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gilliet, M. Targeted therapies and precision medicine for inflammatory skin diseases. Eur. J. Dermatol 29, 19–24 (2019).Article

Gilliet，M。炎症性皮肤病的靶向治疗和精准医学。《欧洲皮肤病杂志》29,19-24（2019）。文章

PubMed

Google Scholar

谷歌学者

Distler, O., Ludwig, R. J., Niemann, S., Riemekasten, G. & Schreiber, S. Editorial: Precision Medicine in Chronic Inflammation. Front Immunol. 12, 770462 (2021).Article

。前免疫。12770462（2021）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Talamonti, M. et al. Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br. J. Dermatol 169, 458–463 (2013).Article

Talamonti，M。等。银屑病的药物遗传学：HLA-Cw6而非LCE3B/3C缺失或TNFAIP3多态性易患白细胞介素12/23阻滞剂ustekinumab的临床反应。Br.J.Dermatol 169458-463（2013）。文章

PubMed

Google Scholar

谷歌学者

Li, K. et al. HLA-C*06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program. J. Invest Dermatol 136, 2364–2371 (2016).Article

Li，K。等人。HLA-C*06:02等位基因和对IL-12/23抑制的反应：来自Ustekinumab 3期牛皮癣计划的结果。J、 Invest Dermatol 1362364–2371（2016）。文章

PubMed

Google Scholar

谷歌学者

Costanzo, A. et al. Secukinumab shows high efficacy irrespective of HLA-Cw6 status in patients with moderate-to-severe plaque-type psoriasis: SUPREME study. Br. J. Dermatol 179, 1072–1080 (2018).Article

Costanzo，A。等人Secukinumab在中重度斑块型银屑病患者中显示出高疗效，而与HLA-Cw6状态无关：SUPREME研究。Br.J.Dermatol 1791072-1080（2018）。文章

PubMed

Google Scholar

谷歌学者

Garzorz-Stark, N. et al. A novel molecular disease classifier for psoriasis and eczema. Exp. Dermatol 25, 767–774 (2016).Article

Garzorz-Stark，N。等人。一种用于牛皮癣和湿疹的新型分子疾病分类器。Exp.Dermatol 25767–774（2016）。文章

PubMed

Google Scholar

谷歌学者

Liu, Y. et al. Classification of human chronic inflammatory skin disease based on single-cell immune profiling. Sci. Immunol. 7, eabl9165 (2022).Article

Liu，Y.等人。基于单细胞免疫分析的人类慢性炎症性皮肤病分类。科学。免疫。7，eabl9165（2022）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schabitz, A. et al. Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases. Nat. Commun. 13, 7729 (2022).Article

Schabitz，A。等人。非传染性炎症性皮肤病病变的空间转录组学景观。国家公社。137729（2022）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Conrad, C. et al. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat. Commun. 9, 25 (2018).Article

在矛盾性银屑病中，TNF阻断剂诱导I型干扰素反应失调而无自身免疫。国家公社。9，25（2018）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhao, L. et al. Evaluation of Dupilumab in Patients With Bullous Pemphigoid. JAMA Dermatol 159, 953–960 (2023).Article

Zhao，L。等人。Dupilumab在大疱性类天疱疮患者中的评估。JAMA Dermatol 159953-960（2023）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Czarnowicki, T., He, H., Krueger, J. G. & Guttman-Yassky, E. Atopic dermatitis endotypes and implications for targeted therapeutics. J. Allergy Clin. Immunol. 143, 1–11 (2019).Article

Czarnowicki，T.，He，H.，Krueger，J.G。＆Guttman-Yassky，E。特应性皮炎内源性及其对靶向治疗的影响。J、过敏临床。免疫。143，1-11（2019）。文章

PubMed

Google Scholar

谷歌学者

Conrad, C. & Gilliet, M. Psoriasis: from Pathogenesis to Targeted Therapies. Clin. Rev. Allergy Immunol. 54, 102–113 (2018).Article

Conrad，C。＆Gilliet，M。牛皮癣：从发病机制到靶向治疗。临床。版本过敏免疫。54102-113（2018）。文章

PubMed

Google Scholar

谷歌学者

Download referencesAcknowledgementsWe thank I. Surbeck, A. Darbellay, and A. Joncic for technical assistance. This work was funded by the Swiss National Science Foundation (310030B_182834, 310030_204835, 4078P0_198470) and the Leenaards Foundation to MG.Author informationAuthor notesThese authors contributed equally: Teofila Seremet, Jeremy Di Domizio, Antoine Girardin.Authors and AffiliationsDepartment of Dermatology, Lausanne University Hospital CHUV and University of Lausanne, 1011, Lausanne, SwitzerlandTeofila Seremet, Jeremy Di Domizio, Antoine Girardin, Ahmad Yatim, Raphael Jenelten, Francesco Messina, Fanny Saidoune, Sofia Bogiatzi, Frederic Minisini, Matthieu Leuenberger, Héloise Wüthrich, Maxime Vernez, Daniel Hohl, Emmanuella Guenova, Curdin Conrad & Michel GillietDepartment of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandChristoph SchlapbachDepartment of Dermatology and Venereology, Medical Center, University of Freiburg, Freiburg, GermanyNatalie Garzorz-Stark, Stefanie Eyerich & Kilian EyerichDepartment of Dermatology and Venereology, CHU Toulouse, Toulouse, FranceCarle PaulBiomedical Data Science Center, CHUV, UNIL, and SIB, Lausanne, SwitzerlandRaphael GottardoAuthorsTeofila SeremetView author publicationsYou can also search for this author in.

下载参考文献致谢我们感谢I.Surbeck，A.Darbellay和A.Joncic提供的技术援助。这项工作由瑞士国家科学基金会（310030B\U 182834、310030\U 204835、4078P0\U 198470）和利纳德基金会资助MG。作者信息作者注意到这些作者做出了同样的贡献：Teofila Seremet，Jeremy Di Domizio，Antoine Girardin。作者和所属机构洛桑大学医院皮肤科CHUV和洛桑大学，1011，洛桑，瑞士特奥菲拉·塞雷梅特，杰里米·迪多米齐奥，安托万·吉拉丁，艾哈迈德·亚蒂姆，拉斐尔·杰内尔顿，弗朗西斯科·梅西纳，范尼·赛杜恩，索非亚·博吉亚茨，弗雷德里克·米西尼，马蒂厄·卢恩贝格，Héloise Wüthrich，马克西姆·韦尔内兹，丹尼尔·霍尔，艾曼纽拉·圭诺娃，柯丁·康拉德和米歇尔·吉利特皮肤科，伯尔尼大学附属医院伯尔尼，伯尔尼，瑞士克里斯托普·施拉巴赫弗赖堡大学医学中心皮肤病学和性病学系，德国弗赖堡大学纳塔利·加佐尔兹·斯塔克，斯蒂芬妮·埃里奇和基利安·埃里奇皮肤病学和性病学系，图卢兹，图卢兹，弗朗西卡利·保罗生物医学数据科学中心，联合利华州丘夫，瑞士洛桑市SIB，瑞士德拉斐尔·戈塔尔多奥菲拉·塞雷梅特维作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarJeremy Di DomizioView author publicationsYou can also search for this author in

PubMed谷歌学者Jeremy Di DomizioView作者出版物您也可以在

PubMed Google ScholarAntoine GirardinView author publicationsYou can also search for this author in

PubMed Google ScholarAntoine GirardinView作者出版物您也可以在

PubMed Google ScholarAhmad YatimView author publicationsYou can also search for this author in

PubMed Google ScholarAhmad YatimView作者出版物您也可以在

PubMed Google ScholarRaphael JeneltenView author publicationsYou can also search for this author in

PubMed Google Scholararphael JeneltenView作者出版物您也可以在

PubMed Google ScholarFrancesco MessinaView author publicationsYou can also search for this author in

PubMed Google ScholarFrancesco MessinaView作者出版物您也可以在

PubMed Google ScholarFanny SaidouneView author publicationsYou can also search for this author in

PubMed谷歌学者Fanny SaidouneView作者出版物您也可以在

PubMed Google ScholarChristoph SchlapbachView author publicationsYou can also search for this author in

PubMed Google ScholarChristoph SchlapbachView作者出版物您也可以在

PubMed Google ScholarSofia BogiatziView author publicationsYou can also search for this author in

PubMed Google ScholarSofia BogiatziView作者出版物您也可以在

PubMed Google ScholarFrederic MinisiniView author publicationsYou can also search for this author in

PubMed谷歌学者Frederic MinisinView作者出版物您也可以在

PubMed Google ScholarNatalie Garzorz-StarkView author publicationsYou can also search for this author in

PubMed Google ScholarNatalie Garzorz StarkView作者出版物您也可以在

PubMed Google ScholarMatthieu LeuenbergerView author publicationsYou can also search for this author in

PubMed Google ScholarMatthieu LeuenbergerView作者出版物您也可以在

PubMed Google ScholarHéloise WüthrichView author publicationsYou can also search for this author in

PubMed Google ScholarHéloise WüthrichView作者出版物您也可以在

PubMed Google ScholarMaxime VernezView author publicationsYou can also search for this author in

PubMed Google ScholarMaxime VernezView作者出版物您也可以在

PubMed Google ScholarDaniel HohlView author publicationsYou can also search for this author in

PubMed Google ScholarDaniel HohlView作者出版物您也可以在

PubMed Google ScholarStefanie EyerichView author publicationsYou can also search for this author in

PubMed Google ScholarStefanie EyerichView作者出版物您也可以在

PubMed Google ScholarKilian EyerichView author publicationsYou can also search for this author in

PubMed Google ScholarKilian EyerichView作者出版物您也可以在

PubMed Google ScholarEmmanuella GuenovaView author publicationsYou can also search for this author in

PubMed Google ScholarEmmanuella Guenoview作者出版物您也可以在

PubMed Google ScholarCarle PaulView author publicationsYou can also search for this author in

PubMed谷歌学者保罗·维尤（PaulView）作者出版物您也可以在

PubMed Google ScholarRaphael GottardoView author publicationsYou can also search for this author in

PubMed Google Scholaraphael GottardoView作者出版物您也可以在

PubMed Google ScholarCurdin ConradView author publicationsYou can also search for this author in

PubMed Google ScholarCurdin ConradView作者出版物您也可以在

PubMed Google ScholarMichel GillietView author publicationsYou can also search for this author in

PubMed Google ScholarMichel GillietView作者出版物您也可以在

PubMed Google ScholarContributionsT.S., J.D.D., and A.G. produced the data. T.S. coordinated patient recruitment and sampling. J.D.D. and A.G. generated nanostring transcriptomics data and associated bioinformatics analysis. A.Y., R.J., F.Me., F.S., C.S., S.B., F.Mi., M.L., H.W., C.P., and C.C.

PubMed谷歌学术贡献者。S、，J.D.D.和A.G.产生了数据。T、。J、 D.D.和A.G.生成了nanostring转录组学数据和相关的生物信息学分析。A、 Y.，R.J.，F.Me.，F.S.，C.S.，S.B.，F.Mi.，M.L.，H.W.，C.P.，和C.C。

selected patients, performed skin biopsies, and analyses. N.G.S, S.E., and K.E. provided RNA sequencing data. M.V., D.H., and E.G. performed histopathological analyses. R.G. supervised the statistics and bioinformatics analyses. M.G. conceived and supervised the work, and wrote the manuscript along with T.S., J.D.D., and A.G.

选择患者，进行皮肤活检和分析。N、 G.S，S.E。和K.E.提供了RNA测序数据。M、 V.，D.H。和E.G.进行了组织病理学分析。R、 G.监督统计和生物信息学分析。M、 G.构思并监督了这项工作，并与T.S.，J.D.D.和A.G.一起撰写了手稿。

as well as comments from co-authors.Corresponding authorCorrespondence to.

以及合著者的评论。对应作者对应。

Michel Gilliet.Ethics declarations

米歇尔·吉利特。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Peer review

同行评审

Peer review information

同行评审信息

Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Nature Communications感谢匿名审稿人对这项工作的同行评审做出的贡献。可以获得同行评审文件。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary InformationReporting SummaryPeer Review fileSource dataSource DataRights and permissions

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充信息报告摘要同行评审文件源数据源数据权限

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

开放获取本文是根据知识共享署名4.0国际许可证授权的，该许可证允许以任何媒体或格式使用，共享，改编，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出是否进行了更改。

The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by/4.0/..

Reprints and permissionsAbout this articleCite this articleSeremet, T., Di Domizio, J., Girardin, A. et al. Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases.

转载和许可本文引用本文Seremet，T.，Di Domizio，J.，Girardin，A。等人的免疫模块来指导炎症性皮肤病的诊断和个性化治疗。

Nat Commun 15, 10688 (2024). https://doi.org/10.1038/s41467-024-54559-6Download citationReceived: 23 April 2024Accepted: 14 November 2024Published: 18 December 2024DOI: https://doi.org/10.1038/s41467-024-54559-6Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Nat Commun 1510688（2024）。https://doi.org/10.1038/s41467-024-54559-6Download引文收到日期：2024年4月23日接受日期：2024年11月14日发布日期：2024年12月18日OI：https://doi.org/10.1038/s41467-024-54559-6Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

全球产业链接平台

重庆市渝北区金星科技大厦A区5楼512室

联系电话：023-67139735（重庆）

关于我们

产品服务