{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:48:24Z","timestamp":1789735704866,"version":"4.0.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"NSFC|National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872877"],"award-info":[{"award-number":["81872877"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC|National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803142"],"award-info":[{"award-number":["81803142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC|National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673436"],"award-info":[{"award-number":["81673436"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC|National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81730100"],"award-info":[{"award-number":["81730100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC|National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91853109"],"award-info":[{"award-number":["91853109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2022,3,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology\u20102 domain\u2010containing protein tyrosine phosphatase\u20102 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)\u2010induced psoriasis\u2010like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro\u2010inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ\u2010triggered skin inflammation in mice. Single\u2010cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ\u2010induced psoriasis\u2010like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)\u2014but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll\u2010like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B\u2010mediated skin inflammation. Importantly,\n                    <jats:italic>Tlr7<\/jats:italic>\n                    point\u2010mutant knock\u2010in mice showed an attenuated psoriasis\u2010like phenotype compared to wild\u2010type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202114455","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T13:37:12Z","timestamp":1640180232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Allosteric inhibition of SHP2 uncovers aberrant TLR7 trafficking in aggravating psoriasis"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-4083","authenticated-orcid":false,"given":"Yuyu","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-6066","authenticated-orcid":false,"given":"Wei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenli","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-2511","authenticated-orcid":false,"given":"Dijun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1425-0089","authenticated-orcid":false,"given":"Yang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"BFEMMM202114455_CR1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.immuni.2006.10.014","volume":"25","author":"H An","year":"2006","unstructured":"An H, Zhao W, Hou J, Zhang Y, Xie Y, Zheng Y, Xu H, Qian C, Zhou J, Yu Y et\u00a0al (2006) SHP\u20102 phosphatase negatively regulates the TRIF adaptor protein\u2010dependent type I interferon and proinflammatory cytokine production. Immunity 25: 919\u2013928","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41586-018-0052-z","volume":"556","author":"M Bambouskova","year":"2018","unstructured":"Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K, Korenfeld D, Mathyer ME, Kim H, Huang L\u2010H et\u00a0al (2018) Electrophilic properties of itaconate and derivatives regulate the I\u03baB\u03b6\u2010ATF3 inflammatory axis. Nature 556: 501\u2013504","journal-title":"Nature"},{"key":"BFEMMM202114455_CR3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-immunol-031210-101340","volume":"29","author":"R Barbalat","year":"2011","unstructured":"Barbalat R, Ewald SE, Mouchess ML, Barton GM (2011) Nucleic acid recognition by the innate immune system. Annu Rev Immunol 29: 185\u2013214","journal-title":"Annu Rev Immunol"},{"key":"BFEMMM202114455_CR4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0969-2126(98)00027-6","volume":"6","author":"D Barford","year":"1998","unstructured":"Barford D, Neel BG (1998) Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP\u20102. Structure 6: 249\u2013254","journal-title":"Structure"},{"key":"BFEMMM202114455_CR5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0002-9343(97)00178-2","volume":"102","author":"KR Beutner","year":"1997","unstructured":"Beutner KR, Tyring S (1997) Human papillomavirus and human disease. Am J Med 102: 9\u201315","journal-title":"Am J Med"},{"key":"BFEMMM202114455_CR6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.immuni.2010.03.012","volume":"32","author":"AL Blasius","year":"2010","unstructured":"Blasius AL, Beutler B (2010) Intracellular toll\u2010like receptors. Immunity 32: 305\u2013315","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR7","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","volume":"386","author":"W\u2010H Boehncke","year":"2015","unstructured":"Boehncke W\u2010H, Sch\u00f6n MP (2015) Psoriasis. Lancet 386: 983\u2013994","journal-title":"Lancet"},{"key":"BFEMMM202114455_CR8","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.immuni.2013.09.002","volume":"39","author":"B Boisson","year":"2013","unstructured":"Boisson B, Wang C, Pedergnana V, Wu L, Cypowyj S, Rybojad M, Belkadi A, Picard C, Abel L, Fieschi C et\u00a0al (2013) A biallelic ACT1 mutation selectively abolishes interleukin\u201017 responses in humans with chronic mucocutaneous candidiasis. Immunity 39: 676\u2013686","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR9","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.jaci.2013.05.036","volume":"132","author":"PM Brunner","year":"2013","unstructured":"Brunner PM, Koszik F, Reininger B, Kalb ML, Bauer W, Stingl G (2013) Infliximab induces downregulation of the IL\u201012\/IL\u201023 axis in 6\u2010sulfo\u2010LacNac (slan)+ dendritic cells and macrophages. J Allergy Clin Immunol 132: 1184\u20131193.e8","journal-title":"J Allergy Clin Immunol"},{"key":"BFEMMM202114455_CR10","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3109\/10409238.2015.1033511","volume":"50","author":"CE Bryant","year":"2015","unstructured":"Bryant CE, Gay NJ, Heymans S, Sacre S, Schaefer L, Midwood KS (2015) Advances in Toll\u2010like receptor biology: modes of activation by diverse stimuli. Crit Rev Biochem Mol Biol 50: 359\u2013379","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"BFEMMM202114455_CR11","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.cell.2016.11.044","volume":"167","author":"PR Burkett","year":"2016","unstructured":"Burkett PR, Kuchroo VK (2016) IL\u201017 Blockade in psoriasis. Cell 167: 1669","journal-title":"Cell"},{"key":"BFEMMM202114455_CR12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler A, Hoffman P, Smibert P, Papalexi E, Satija R (2018) Integrating single\u2010cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol 36: 411\u2013420","journal-title":"Nat Biotechnol"},{"key":"BFEMMM202114455_CR13","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1111\/jdv.13521","volume":"30","author":"A Catharino","year":"2016","unstructured":"Catharino A, Daiha E, Carvalho C, Martinez D, Lima RB, D\u2019Acri A, Martins CJ, Lupi O (2016) Possible correlations between annular pustular psoriasis and Noonan syndrome. J Eur Acad Dermatol Venereol 30: e195\u2013e196","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"BFEMMM202114455_CR14","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1084\/jem.20062648","volume":"204","author":"ML Caton","year":"2007","unstructured":"Caton ML, Smith\u2010Raska MR, Reizis B (2007) Notch\u2010RBP\u2010J signaling controls the homeostasis of CD8\u2010 dendritic cells in the spleen. J Exp Med 204: 1653\u20131664","journal-title":"J Exp Med"},{"key":"BFEMMM202114455_CR15","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cytogfr.2014.06.002","volume":"25","author":"S Chattopadhyay","year":"2014","unstructured":"Chattopadhyay S, Sen GC (2014) Tyrosine phosphorylation in Toll\u2010like receptor signaling. Cytokine Growth Factor Rev 25: 533\u2013541","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFEMMM202114455_CR16","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nature18621","volume":"535","author":"Y\u2010N Chen","year":"2016","unstructured":"Chen Y\u2010N, LaMarche MJ, Chan HM, Fekkes P, Garcia\u2010Fortanet J, Acker MG, Antonakos B, Chen C\u2010T, Chen Z, Cooke VG et\u00a0al (2016) Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature 535: 148\u2013152","journal-title":"Nature"},{"key":"BFEMMM202114455_CR17","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.3389\/fimmu.2019.02376","volume":"10","author":"C\u2010C Chiang","year":"2019","unstructured":"Chiang C\u2010C, Cheng W\u2010J, Korinek M, Lin C\u2010Y, Hwang T\u2010L (2019) Neutrophils in Psoriasis. Front Immunol 10: 2376","journal-title":"Front Immunol"},{"key":"BFEMMM202114455_CR18","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.chom.2012.02.002","volume":"11","author":"C\u2010Y Chiang","year":"2012","unstructured":"Chiang C\u2010Y, Engel A, Opaluch A, Ramos I, Maestre A, Secundino I, De\u00a0Jesus P, Nguyen Q, Welch G, Bonamy G et\u00a0al (2012) Cofactors required for TLR7\u2010 and TLR9\u2010dependent innate immune responses. Cell Host Microbe 11: 306\u2013318","journal-title":"Cell Host Microbe"},{"key":"BFEMMM202114455_CR19","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1038\/492S50a","volume":"492","author":"JM Crow","year":"2012","unstructured":"Crow JM (2012) Psoriasis uncovered. Nature 492: S50\u201351","journal-title":"Nature"},{"key":"BFEMMM202114455_CR20","first-page":"3651","volume":"120","author":"O Demaria","year":"2010","unstructured":"Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, Valenzuela DM, Yancopoulos GD, Flavell RA, Alexopoulou L (2010) TLR8 deficiency leads to autoimmunity in mice. J Clin Invest 120: 3651\u20133662","journal-title":"J Clin Invest"},{"key":"BFEMMM202114455_CR21","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ni.3155","volume":"16","author":"Z Deng","year":"2015","unstructured":"Deng Z, Ma S, Zhou H, Zang A, Fang Y, Li T, Shi H, Liu M, Du M, Taylor PR et\u00a0al (2015) Tyrosine phosphatase SHP\u20102 mediates C\u2010type lectin receptor\u2010induced activation of the kinase Syk and anti\u2010fungal TH17 responses. Nat Immunol 16: 642\u2013652","journal-title":"Nat Immunol"},{"key":"BFEMMM202114455_CR22","doi-asserted-by":"crossref","unstructured":"Ding Y, Qu J, Zhang C, Zhu Y, Xu Q, Sun Y (2021) SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis. medRxivhttps:\/\/doi.org\/10.1101\/2021.11.10.21266198 [PREPRINT]","DOI":"10.1101\/2021.11.10.21266198"},{"key":"BFEMMM202114455_CR23","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.immuni.2016.10.010","volume":"45","author":"V Durai","year":"2016","unstructured":"Durai V, Murphy KM (2016) Functions of murine dendritic cells. Immunity 45: 719\u2013736","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR24","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1093\/nar\/gkab043","volume":"49","author":"M Elosua\u2010Bayes","year":"2021","unstructured":"Elosua\u2010Bayes M, Nieto P, Mereu E, Gut I, Heyn H (2021) SPOTlight: seeded NMF regression to deconvolute spatial transcriptomics spots with single\u2010cell transcriptomes. Nucleic Acids Res 49: e50","journal-title":"Nucleic Acids Res"},{"key":"BFEMMM202114455_CR25","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1126\/science.8096088","volume":"259","author":"GS Feng","year":"1993","unstructured":"Feng GS, Hui CC, Pawson T (1993) SH2\u2010containing phosphotyrosine phosphatase as a target of protein\u2010tyrosine kinases. Science 259: 1607\u20131611","journal-title":"Science"},{"key":"BFEMMM202114455_CR26","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1084\/jem.20090480","volume":"206","author":"D Ganguly","year":"2009","unstructured":"Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M (2009) Self\u2010RNA\u2013antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206: 1983\u20131994","journal-title":"J Exp Med"},{"key":"BFEMMM202114455_CR27","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1001\/archderm.140.12.1490","volume":"140","author":"M Gilliet","year":"2004","unstructured":"Gilliet M, Conrad C, Geiges M, Cozzio A, Th\u00fcrlimann W, Burg G, Nestle FO, Dummer R (2004) Psoriasis triggered by toll\u2010like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 140: 1490\u20131495","journal-title":"Arch Dermatol"},{"key":"BFEMMM202114455_CR28","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1038\/s41467-017-02351-0","volume":"8","author":"W Guo","year":"2017","unstructured":"Guo W, Liu W, Chen Z, Gu Y, Peng S, Shen L, Shen Y, Wang X, Feng G\u2010S, Sun Y et\u00a0al (2017) Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1\u2010dependent mitochondrial homeostasis. Nat Commun 8: 2168","journal-title":"Nat Commun"},{"key":"BFEMMM202114455_CR29","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","volume":"20","author":"C Hafemeister","year":"2019","unstructured":"Hafemeister C, Satija R (2019) Normalization and variance stabilization of single\u2010cell RNA\u2010seq data using regularized negative binomial regression. Genome Biol 20: 296","journal-title":"Genome Biol"},{"key":"BFEMMM202114455_CR30","doi-asserted-by":"crossref","first-page":"23977","DOI":"10.1038\/srep23977","volume":"6","author":"Y Hu","year":"2016","unstructured":"Hu Y, Cong X, Chen L, Qi J, Wu X, Zhou M, Yoo D, Li F, Sun W, Wu J et\u00a0al (2016) Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF\/MyD88\u2010NF\u2010\u03baB signaling pathway. Sci Rep 6: 23977","journal-title":"Sci Rep"},{"key":"BFEMMM202114455_CR31","doi-asserted-by":"crossref","first-page":"13241","DOI":"10.1096\/fj.201900642R","volume":"33","author":"M Jiang","year":"2019","unstructured":"Jiang M, Fang H, Shao S, Dang E, Zhang J, Qiao P, Yang A, Wang G (2019) Keratinocyte exosomes activate neutrophils and enhance skin inflammation in psoriasis. FASEB J 33: 13241\u201313253","journal-title":"FASEB J"},{"key":"BFEMMM202114455_CR32","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/eji.201948456","volume":"50","author":"D Kadekar","year":"2020","unstructured":"Kadekar D, Agerholm R, Vi\u00f1als MT, Rizk J, Bekiaris V (2020) The immune checkpoint receptor associated phosphatases SHP\u20101 and SHP\u20102 are not required for \u03b3\u03b4T17 cell development, activation, or skin inflammation. Eur J Immunol 50: 873\u2013879","journal-title":"Eur J Immunol"},{"key":"BFEMMM202114455_CR33","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1111\/exd.13746","volume":"27","author":"H Katayama","year":"2018","unstructured":"Katayama H (2018) Development of psoriasis by continuous neutrophil infiltration into the epidermis. Exp Dermatol 27: 1084\u20131091","journal-title":"Exp Dermatol"},{"key":"BFEMMM202114455_CR34","doi-asserted-by":"crossref","first-page":"30984","DOI":"10.1074\/jbc.M504699200","volume":"280","author":"H Keilhack","year":"2005","unstructured":"Keilhack H, David FS, McGregor M, Cantley LC, Neel BG (2005) Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes. J Biol Chem 280: 30984\u201330993","journal-title":"J Biol Chem"},{"key":"BFEMMM202114455_CR35","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1016\/j.jid.2018.03.1509","volume":"138","author":"HJ Kim","year":"2018","unstructured":"Kim HJ, Roh JY, Jung Y (2018) Eosinophils accelerate pathogenesis of psoriasis by supporting an inflammatory milieu that promotes neutrophil infiltration. J Invest Dermatol 138: 2185\u20132194","journal-title":"J Invest Dermatol"},{"key":"BFEMMM202114455_CR36","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature14175","volume":"521","author":"T Kopp","year":"2015","unstructured":"Kopp T, Riedl E, Bangert C, Bowman EP, Greisenegger E, Horowitz A, Kittler H, Blumenschein WM, McClanahan TK, Marbury T et\u00a0al (2015) Clinical improvement in psoriasis with specific targeting of interleukin\u201023. Nature 521: 222\u2013226","journal-title":"Nature"},{"key":"BFEMMM202114455_CR37","doi-asserted-by":"crossref","first-page":"ITC49\u2013ITC64","DOI":"10.7326\/AITC201804030","volume":"168","author":"M Lebwohl","year":"2018","unstructured":"Lebwohl M (2018) Psoriasis. Ann Intern Med 168: ITC49\u2013ITC64","journal-title":"Ann Intern Med"},{"key":"BFEMMM202114455_CR38","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S0140-6736(19)31513-2","volume":"394","author":"M Lebwohl","year":"2019","unstructured":"Lebwohl M (2019) Interleukin\u201023 blockade: another breakthrough in the treatment of psoriasis. Lancet 394: 544\u2013546","journal-title":"Lancet"},{"key":"BFEMMM202114455_CR39","doi-asserted-by":"crossref","first-page":"490","DOI":"10.4049\/jimmunol.1100123","volume":"187","author":"AM Lin","year":"2011","unstructured":"Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, Villanueva EC, Shah P, Kaplan MJ, Bruce AT (2011) Mast cells and neutrophils release IL\u201017 through extracellular trap formation in psoriasis. J Immunol 187: 490\u2013500","journal-title":"J Immunol"},{"key":"BFEMMM202114455_CR40","doi-asserted-by":"crossref","first-page":"E1362","DOI":"10.1073\/pnas.1518976113","volume":"113","author":"ZR Newman","year":"2016","unstructured":"Newman ZR, Young JM, Ingolia NT, Barton GM (2016) Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9. Proc Natl Acad Sci USA 113: E1362\u20131371","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM202114455_CR41","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-pathol-011811-132448","volume":"7","author":"GK Perera","year":"2012","unstructured":"Perera GK, Di Meglio P, Nestle FO (2012) Psoriasis. Annu Rev Pathol 7: 385\u2013422","journal-title":"Annu Rev Pathol"},{"key":"BFEMMM202114455_CR42","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3389\/fimmu.2017.01075","volume":"8","author":"C Petes","year":"2017","unstructured":"Petes C, Odoardi N, Gee K (2017) The toll for trafficking: toll\u2010like receptor 7 delivery to the endosome. Front Immunol 8: 1075","journal-title":"Front Immunol"},{"key":"BFEMMM202114455_CR43","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0167-4889(02)00322-1","volume":"1592","author":"C\u2010K Qu","year":"2002","unstructured":"Qu C\u2010K (2002) Role of the SHP\u20102 tyrosine phosphatase in cytokine\u2010induced signaling and cellular response. Biochim Biophys Acta 1592: 297\u2013301","journal-title":"Biochim Biophys Acta"},{"key":"BFEMMM202114455_CR44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nature13199","volume":"510","author":"L Riol\u2010Blanco","year":"2014","unstructured":"Riol\u2010Blanco L, Ordovas\u2010Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, Paust S, Wood JN, von Andrian UH (2014) Nociceptive sensory neurons drive interleukin\u201023\u2010mediated psoriasiform skin inflammation. Nature 510: 157\u2013161","journal-title":"Nature"},{"key":"BFEMMM202114455_CR45","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.4049\/jimmunol.1001001","volume":"186","author":"HL Rizzo","year":"2011","unstructured":"Rizzo HL, Kagami S, Phillips KG, Kurtz SE, Jacques SL, Blauvelt A (2011) IL\u201023\u2010mediated psoriasis\u2010like epidermal hyperplasia is dependent on IL\u201017A. J Immunol 186: 1495\u20131502","journal-title":"J Immunol"},{"key":"BFEMMM202114455_CR46","doi-asserted-by":"crossref","first-page":"eaan4730","DOI":"10.1126\/scitranslmed.aan4730","volume":"9","author":"AK Shalek","year":"2017","unstructured":"Shalek AK, Benson M (2017) Single\u2010cell analyses to tailor treatments. Sci Transl Med 9: eaan4730","journal-title":"Sci Transl Med"},{"key":"BFEMMM202114455_CR47","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.bcp.2016.06.001","volume":"115","author":"F Shao","year":"2016","unstructured":"Shao F, Tan T, Tan Y, Sun Y, Wu X, Xu Q (2016) Andrographolide alleviates imiquimod\u2010induced psoriasis in mice via inducing autophagic proteolysis of MyD88. Biochem Pharmacol 115: 94\u2013103","journal-title":"Biochem Pharmacol"},{"key":"BFEMMM202114455_CR48","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jaci.2016.07.025","volume":"139","author":"A Srivastava","year":"2017","unstructured":"Srivastava A, Nikamo P, Lohcharoenkal W, Li D, Meisgen F, Xu Land\u00e9n N, St\u00e5hle M, Pivarcsi A, Sonkoly E (2017) MicroRNA\u2010146a suppresses IL\u201017\u2010mediated skin inflammation and is genetically associated with psoriasis. J Allergy Clin Immunol 139: 550\u2013561","journal-title":"J Allergy Clin Immunol"},{"key":"BFEMMM202114455_CR49","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM, Hao Y, Stoeckius M, Smibert P, Satija R (2019) Comprehensive integration of single\u2010cell data. Cell 177: 1888\u20131902.e21","journal-title":"Cell"},{"key":"BFEMMM202114455_CR50","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta\u2010Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P et\u00a0al (2019) STRING v11: protein\u2010protein association networks with increased coverage, supporting functional discovery in genome\u2010wide experimental datasets. Nucleic Acids Res 47: D607\u2013D613","journal-title":"Nucleic Acids Res"},{"key":"BFEMMM202114455_CR51","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ejmg.2015.08.005","volume":"58","author":"M Tajan","year":"2015","unstructured":"Tajan M, de Rocca SA, Valet P, Edouard T, Yart A (2015) SHP2 sails from physiology to pathology. Eur J Med Genet 58: 509\u2013525","journal-title":"Eur J Med Genet"},{"key":"BFEMMM202114455_CR52","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4049\/jimmunol.1700995","volume":"200","author":"M Tanaka","year":"2018","unstructured":"Tanaka M, Kobiyama K, Honda T, Uchio\u2010Yamada K, Natsume\u2010Kitatani Y, Mizuguchi K, Kabashima K, Ishii KJ (2018) Essential role of CARD14 in murine experimental psoriasis. J Immunol 200: 71\u201381","journal-title":"J Immunol"},{"key":"BFEMMM202114455_CR53","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","volume":"182","author":"L van der Fits","year":"2009","unstructured":"van der Fits L, Mourits S, Voerman JSA, Kant M, Boon L, Laman JD, Cornelissen F, Mus A\u2010M, Florencia E, Prens EP et\u00a0al (2009) Imiquimod\u2010induced psoriasis\u2010like skin inflammation in mice is mediated via the IL\u201023\/IL\u201017 axis. J Immunol 182: 5836\u20135845","journal-title":"J Immunol"},{"key":"BFEMMM202114455_CR54","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/1346-8138.15184","volume":"47","author":"A Wang","year":"2020","unstructured":"Wang A, Bai Y (2020) Dendritic cells: the driver of psoriasis. J Dermatol 47: 104\u2013113","journal-title":"J Dermatol"},{"key":"BFEMMM202114455_CR55","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1172\/JCI87037","volume":"126","author":"J Wang","year":"2016","unstructured":"Wang J, Mizui M, Zeng L\u2010F, Bronson R, Finnell M, Terhorst C, Kyttaris VC, Tsokos GC, Zhang Z\u2010Y, Kontaridis MI (2016) Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus. J Clin Invest 126: 2077\u20132092","journal-title":"J Clin Invest"},{"key":"BFEMMM202114455_CR56","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.immuni.2018.05.012","volume":"49","author":"M Wang","year":"2018","unstructured":"Wang M, Zhang S, Zheng G, Huang J, Songyang Z, Zhao X, Lin X (2018) Gain\u2010of\u2010function mutation of card14 leads to spontaneous psoriasis\u2010like skin inflammation through enhanced keratinocyte response to IL\u201017A. Immunity 49: 66\u201379.e5","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR57","doi-asserted-by":"crossref","first-page":"3709749","DOI":"10.1155\/2020\/3709749","volume":"2020","author":"W\u2010M Wang","year":"2020","unstructured":"Wang W\u2010M, Jin H\u2010Z (2020) Role of neutrophils in psoriasis. J Immunol Res 2020: 3709749","journal-title":"J Immunol Res"},{"key":"BFEMMM202114455_CR58","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1021\/acs.accounts.9b00631","volume":"53","author":"Y Wang","year":"2020","unstructured":"Wang Y, Zhang S, Li H, Wang H, Zhang T, Hutchinson MR, Yin H, Wang X (2020) Small\u2010molecule modulators of toll\u2010like receptors. Acc Chem Res 53: 1046\u20131055","journal-title":"Acc Chem Res"},{"key":"BFEMMM202114455_CR59","doi-asserted-by":"crossref","first-page":"E6795","DOI":"10.3390\/ijms21186795","volume":"21","author":"P W\u00f3jcik","year":"2020","unstructured":"W\u00f3jcik P, Garley M, Wro\u0144ski A, Jab\u0142o\u0144ska E, Skrzydlewska E (2020) Cannabidiol modifies the formation of NETs in neutrophils of psoriatic patients. Int J Mol Sci 21: E6795","journal-title":"Int J Mol Sci"},{"key":"BFEMMM202114455_CR60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1440-0960.2004.00030.x","volume":"45","author":"JK Wu","year":"2004","unstructured":"Wu JK, Siller G, Strutton G (2004) Psoriasis induced by topical imiquimod. Australas J Dermatol 45: 47\u201350","journal-title":"Australas J Dermatol"},{"key":"BFEMMM202114455_CR61","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1172\/JCI97426","volume":"128","author":"R Wu","year":"2018","unstructured":"Wu R, Zeng J, Yuan J, Deng X, Huang YI, Chen L, Zhang P, Feng H, Liu Z, Wang Z et\u00a0al (2018) MicroRNA\u2010210 overexpression promotes psoriasis\u2010like inflammation by inducing Th1 and Th17 cell differentiation. J Clin Invest 128: 2551\u20132568","journal-title":"J Clin Invest"},{"key":"BFEMMM202114455_CR62","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1084\/jem.20181198","volume":"216","author":"P Xiao","year":"2019","unstructured":"Xiao P, Zhang H, Zhang Y, Zheng M, Liu R, Zhao Y, Zhang X, Cheng H, Cao Q, Ke Y (2019) Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin\u201010. J Exp Med 216: 337\u2013349","journal-title":"J Exp Med"},{"key":"BFEMMM202114455_CR63","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.immuni.2018.03.019","volume":"48","author":"M Xu","year":"2018","unstructured":"Xu M, Lu H, Lee Y\u2010H, Wu Y, Liu K, Shi Y, An H, Zhang J, Wang X, Lai Y et\u00a0al (2018) An interleukin\u201025\u2010mediated autoregulatory circuit in keratinocytes plays a pivotal role in psoriatic skin inflammation. Immunity 48: 787\u2013798.e4","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR64","doi-asserted-by":"crossref","first-page":"7652","DOI":"10.1038\/ncomms8652","volume":"6","author":"S Yan","year":"2015","unstructured":"Yan S, Xu Z, Lou F, Zhang L, Ke F, Bai J, Liu Z, Liu J, Wang H, Zhu H et\u00a0al (2015) NF\u2010\u03baB\u2010induced microRNA\u201031 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun 6: 7652","journal-title":"Nat Commun"},{"key":"BFEMMM202114455_CR65","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.3390\/molecules24112157","volume":"24","author":"B\u2010Y Yang","year":"2019","unstructured":"Yang B\u2010Y, Cheng Y\u2010G, Liu Y, Liu Y, Tan J\u2010Y, Guan W, Guo S, Kuang H\u2010X (2019) Datura Metel L. Ameliorates imiquimod\u2010induced psoriasis\u2010like dermatitis and inhibits inflammatory cytokines production through TLR7\/8\u2010MyD88\u2010NF\u2010\u03baB\u2010NLRP3 inflammasome pathway. Molecules 24: 2157","journal-title":"Molecules"},{"key":"BFEMMM202114455_CR66","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L\u2010G, Han Y, He Q\u2010Y (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16: 284\u2013287","journal-title":"OMICS"},{"key":"BFEMMM202114455_CR67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.immuni.2016.06.021","volume":"45","author":"L\u2010J Zhang","year":"2016","unstructured":"Zhang L\u2010J, Sen G, Ward N, Johnston A, Chun K, Chen Y, Adase C, Sanford J, Gao N, Chensee M et\u00a0al (2016) Antimicrobial peptide LL37 and MAVS signaling drive interferon\u2010\u03b2 production by epidermal keratinocytes during skin injury. Immunity 45: 119\u2013130","journal-title":"Immunity"},{"key":"BFEMMM202114455_CR68","doi-asserted-by":"crossref","first-page":"589","DOI":"10.15252\/emmm.201607027","volume":"9","author":"H Zhu","year":"2017","unstructured":"Zhu H, Lou F, Yin Q, Gao Y, Sun Y, Bai J, Xu Z, Liu Z, Cai W, Ke F et\u00a0al (2017) RIG\u2010I antiviral signaling drives interleukin\u201023 production and psoriasis\u2010like skin disease. EMBO Mol Med 9: 589\u2013604","journal-title":"EMBO Mol Med"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202114455.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.202114455","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.202114455\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.202114455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202114455.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:35:57Z","timestamp":1779086157000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.202114455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":68,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3,7]]}},"alternative-id":["BFEMMM202114455"],"URL":"https:\/\/doi.org\/10.15252\/emmm.202114455","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]},"assertion":[{"value":"26 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Y. Sun and Q. Xu have a patent pending on use of SHP2 inhibitors in psoriasis (202010109716.0). The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMMM202114455"}}