S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3

Immunity
Helia B SchonthalerErwin F Wagner

Abstract

Psoriasis is a common heterogeneous inflammatory skin disease with a complex pathophysiology and limited treatment options. Here we performed proteomic analyses of human psoriatic epidermis and found S100A8-S100A9, also called calprotectin, as the most upregulated proteins, followed by the complement component C3. Both S100A8-S100A9 and C3 are specifically expressed in lesional psoriatic skin. S100A9 is shown here to function as a chromatin component modulating C3 expression in mouse and human cells by binding to a region upstream of the C3 start site. When S100A9 was genetically deleted in mouse models of skin inflammation, the psoriasis-like skin disease and inflammation were strongly attenuated, with a mild immune infiltrate and decreased amounts of C3. In addition, inhibition of C3 in the mouse model strongly reduced the inflammatory skin disease. Thus, S100A8-S100A9 can regulate C3 at the nuclear level and present potential new therapeutic targets for psoriasis.

References

Sep 1, 1989·The British Journal of Dermatology·F Acevedo, H Hammar
Jan 1, 1989·Human Heredity·R J WyattE W Rosenberg
Dec 1, 1993·The Journal of Investigative Dermatology·N Basset-SéguinJ J Guilhou
Jan 5, 2000·The Journal of Investigative Dermatology·H SuzukiD N Sauder
Sep 7, 2000·Biochemical and Biophysical Research Communications·M J Robinson, N Hogg
Sep 5, 2002·The British Journal of Dermatology·V GurminH L C Beynon
Mar 18, 2003·Molecular and Cellular Biology·Josie A R HobbsNancy Hogg
Mar 20, 2003·Microscopy Research and Technique·Wolfgang NackenClaus Kerkhoff
May 30, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tiphaine MonsinjonMarc C Fontaine
May 20, 2004·JAMA : the Journal of the American Medical Association·Marinos C Dalakas
Aug 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francesca PalamaraMaria Sibilia
May 13, 2006·Journal of Molecular Biology·Nadja LeukertJohannes Roth
Jul 19, 2006·Biochemical Pharmacology·Christoffer GebhardtJochen Hess
Oct 20, 2006·Biochimica Et Biophysica Acta·Thomas VoglJohannes Roth
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francisco LeonBrian L Kelsall
Feb 23, 2007·Nature·Michelle A LowesJames G Krueger
May 2, 2007·Nature Clinical Practice. Rheumatology·Jagadeesh BayrySrini V Kaveri
Jul 21, 2007·The American Journal of Pathology·Maciej M Markiewski, John D Lambris
Nov 22, 2007·Molecular & Cellular Proteomics : MCP·Laurent BarbeHelene Andersson-Svahn
Jan 23, 2008·The Journal of Experimental Medicine·Christoffer GebhardtPeter Angel
Jan 30, 2008·Arthritis Research & Therapy·Rainer ZenzErwin F Wagner
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emma Guttman-YasskyJames G Krueger
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leslie van der FitsErik Lubberts
Jul 31, 2009·The New England Journal of Medicine·Frank O NestleJonathan Barker
Aug 12, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Julia NémethJochen Hess
Nov 26, 2009·Genes & Development·Juan Guinea-ViniegraErwin F Wagner
Dec 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Helia B SchonthalerErwin F Wagner
Mar 23, 2010·Cell·Sergei I GrivennikovMichael Karin
Jul 21, 2010·Nature Immunology·Mahima SwamyAdrian Hayday
Sep 30, 2010·Nature Reviews. Rheumatology·Erwin F WagnerErwin Tschachler
Dec 15, 2010·Science Translational Medicine·Ronald WolfStuart H Yuspa
Oct 22, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J R BakerN Hogg
Dec 14, 2011·The Journal of Investigative Dermatology·Teruaki Nakatsuji, Richard L Gallo
Dec 27, 2011·Immunity·Paola Di MeglioFrank O Nestle
Mar 1, 2012·Nature Reviews. Cancer·Esther N ArwertFiona M Watt
Aug 14, 2012·Experimental Dermatology·Claus KerkhoffKarin E Bornfeldt

❮ Previous
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Citations

May 23, 2014·Archives of Dermatological Research·Tiago TorresManuela Selores
Dec 23, 2015·Chemical Research in Toxicology·Arnold S GroehlerNatalia Y Tretyakova
Sep 13, 2015·Genomics, Proteomics & Bioinformatics·Shan JiangTianfu Wu
Jul 3, 2015·International Journal of Cancer. Journal International Du Cancer·Xuemei ZhangJian Ma
Oct 7, 2015·The Journal of Experimental Medicine·Kei YamamotoMakoto Murakami
Apr 12, 2016·Journal of Proteomics·J ReindlH Rhode
Oct 11, 2014·International Journal of Cancer. Journal International Du Cancer·Sonja FunkJochen Hess
Apr 22, 2015·Nature Communications·Monika PruensterMarkus Sperandio
Feb 7, 2015·Journal of Dermatological Science·Yu-An CaoRoger L Kaspar
Dec 20, 2014·Cell Death and Differentiation·M K ThomsenE F Wagner
May 26, 2016·Nature Communications·Hani AlrefaiEdgar Serfling
Aug 6, 2016·Pharmacology & Therapeutics·Monika PruensterMarkus Sperandio
Jul 2, 2016·The Journal of Investigative Dermatology·Joan ManilsConcepció Soler
Oct 25, 2016·The Journal of Investigative Dermatology·Nicole AmbergMaria Sibilia
Sep 2, 2016·International Immunopharmacology·Xuguo WangJinhong Hu
Oct 5, 2016·Scientific Reports·Hiroki TanigawaYuichi Oike
Sep 22, 2016·The FEBS Journal·Özge Uluçkan, Erwin F Wagner
Oct 6, 2016·Expert Review of Clinical Immunology·Maureen C TurinaDominique Baeten
Nov 24, 2016·The Journal of Investigative Dermatology·Chiara GiacomassiMarina Botto
Oct 16, 2014·Molecular & Cellular Proteomics : MCP·Dequina NicholasKangling Zhang
Apr 2, 2018·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·F D'AmicoM C Mazzarino
Nov 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erika SuzukiIannis E Adamopoulos
Nov 17, 2017·Nature Immunology·George HajishengallisJohn D Lambris
Nov 22, 2017·Scientific Reports·Archana BajpaiHiroaki Kitano
Sep 30, 2016·The Journal of International Medical Research·Maria Sole ChimentiAntonio Costanzo
May 8, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yong TangXin Lin
May 10, 2016·F1000Research·Franziska C EberleKamran Ghoreschi
Feb 6, 2019·International Immunology·Shoiab BukhariShruti Naik
Mar 25, 2019·Experimental Dermatology·Jingling ZhaoSeok Jong Hong
May 3, 2019·Nature Reviews. Immunology·Edimara S ReisJohn D Lambris
Sep 14, 2014·EMBO Molecular Medicine·Elisabeth GlitznerMaria Sibilia
Jan 4, 2018·Blood Advances·Yuya YoshiokaMasahiko Sugita
Nov 7, 2019·Experimental Dermatology·David GrandJohn W Frew

❮ Previous
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