IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema
Background Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear. Objective We sought to characterize the role of IL‐17C in human ISD. Methods IL‐17C gene and protei...
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| Veröffentlicht in: | JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY 2020-04, Vol.34 (4), p.800-809 |
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| creator | Lauffer, F. Jargosch, M. Baghin, V. Krause, L. Kempf, W. Absmaier‐Kijak, M. Morelli, M. Madonna, S. Marsais, F. Lepescheux, L. Albanesi, C. Müller, N.S. Theis, F.J. Schmidt‐Weber, C. Eyerich, S. Biedermann, T. Vandeghinste, N. Steidl, S. Eyerich, K. |
| description | Background
Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear.
Objective
We sought to characterize the role of IL‐17C in human ISD.
Methods
IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined.
Results
Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo.
Conclusion
IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD. |
| doi_str_mv | 10.1111/jdv.16126 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2320873740</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2320873740</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4646-428e4d356207a4b5061814e48155190c1d75e99223e2f35d6c4311e268f6223a3</originalsourceid><addsrcrecordid>eNp1kLtOw0AQRVcIREKg4AeQSyic7OzLdonCKyhSGqBdbeyxssEvvDFRqPgEvpEvwcEhHdPMzNXRKS4h50CH0M5ombwPQQFTB6QPQoU-pyE_JH0aMeVHkYx65MS5JaUUQIbHpMchiDhQ2SezyfT78wuCsWfyKrOpRedhZVcLzKzJPFukmclzs7Jl0T7eoslN4VWurK1x1nmmSDyzKisbexh_YG5OyVFqModnuz0gz3e3T-MHfzq7n4yvp34slFC-YCGKhEvFaGDEXFIFIQgUIUgJEY0hCSRGEWMcWcplomLBAZCpMFVtaPiA-J3XrbFq5rqqbW7qjS6N1bvotb1Qi0AyoC1_2fFVXb416FY6ty7GLDMFlo3TjDMaBjwQW_SqQ-O6dK7GdC8Hqrd967Zv_dt3y17stM08x2RP_hXcAqMOWNsMN_-b9OPNS6f8AYRoiNw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2320873740</pqid></control><display><type>article</type><title>IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Lauffer, F. ; Jargosch, M. ; Baghin, V. ; Krause, L. ; Kempf, W. ; Absmaier‐Kijak, M. ; Morelli, M. ; Madonna, S. ; Marsais, F. ; Lepescheux, L. ; Albanesi, C. ; Müller, N.S. ; Theis, F.J. ; Schmidt‐Weber, C. ; Eyerich, S. ; Biedermann, T. ; Vandeghinste, N. ; Steidl, S. ; Eyerich, K.</creator><creatorcontrib>Lauffer, F. ; Jargosch, M. ; Baghin, V. ; Krause, L. ; Kempf, W. ; Absmaier‐Kijak, M. ; Morelli, M. ; Madonna, S. ; Marsais, F. ; Lepescheux, L. ; Albanesi, C. ; Müller, N.S. ; Theis, F.J. ; Schmidt‐Weber, C. ; Eyerich, S. ; Biedermann, T. ; Vandeghinste, N. ; Steidl, S. ; Eyerich, K.</creatorcontrib><description>Background
Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear.
Objective
We sought to characterize the role of IL‐17C in human ISD.
Methods
IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined.
Results
Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo.
Conclusion
IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.</description><identifier>ISSN: 0926-9959</identifier><identifier>EISSN: 1468-3083</identifier><identifier>DOI: 10.1111/jdv.16126</identifier><identifier>PMID: 31793105</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Cell Movement ; Dermatitis, Atopic - immunology ; Disease Models, Animal ; Gene Expression ; Humans ; Inflammation - immunology ; Interleukin-17 - immunology ; Keratinocytes - immunology ; Mice ; Neutrophils - immunology ; Psoriasis - immunology ; Th17 Cells - immunology ; Th2 Cells - immunology</subject><ispartof>JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2020-04, Vol.34 (4), p.800-809</ispartof><rights>2019 European Academy of Dermatology and Venereology</rights><rights>2019 European Academy of Dermatology and Venereology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4646-428e4d356207a4b5061814e48155190c1d75e99223e2f35d6c4311e268f6223a3</citedby><cites>FETCH-LOGICAL-c4646-428e4d356207a4b5061814e48155190c1d75e99223e2f35d6c4311e268f6223a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjdv.16126$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjdv.16126$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31793105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:142786119$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Lauffer, F.</creatorcontrib><creatorcontrib>Jargosch, M.</creatorcontrib><creatorcontrib>Baghin, V.</creatorcontrib><creatorcontrib>Krause, L.</creatorcontrib><creatorcontrib>Kempf, W.</creatorcontrib><creatorcontrib>Absmaier‐Kijak, M.</creatorcontrib><creatorcontrib>Morelli, M.</creatorcontrib><creatorcontrib>Madonna, S.</creatorcontrib><creatorcontrib>Marsais, F.</creatorcontrib><creatorcontrib>Lepescheux, L.</creatorcontrib><creatorcontrib>Albanesi, C.</creatorcontrib><creatorcontrib>Müller, N.S.</creatorcontrib><creatorcontrib>Theis, F.J.</creatorcontrib><creatorcontrib>Schmidt‐Weber, C.</creatorcontrib><creatorcontrib>Eyerich, S.</creatorcontrib><creatorcontrib>Biedermann, T.</creatorcontrib><creatorcontrib>Vandeghinste, N.</creatorcontrib><creatorcontrib>Steidl, S.</creatorcontrib><creatorcontrib>Eyerich, K.</creatorcontrib><title>IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema</title><title>JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY</title><addtitle>J Eur Acad Dermatol Venereol</addtitle><description>Background
Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear.
Objective
We sought to characterize the role of IL‐17C in human ISD.
Methods
IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined.
Results
Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo.
Conclusion
IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.</description><subject>Animals</subject><subject>Cell Movement</subject><subject>Dermatitis, Atopic - immunology</subject><subject>Disease Models, Animal</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Inflammation - immunology</subject><subject>Interleukin-17 - immunology</subject><subject>Keratinocytes - immunology</subject><subject>Mice</subject><subject>Neutrophils - immunology</subject><subject>Psoriasis - immunology</subject><subject>Th17 Cells - immunology</subject><subject>Th2 Cells - immunology</subject><issn>0926-9959</issn><issn>1468-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLtOw0AQRVcIREKg4AeQSyic7OzLdonCKyhSGqBdbeyxssEvvDFRqPgEvpEvwcEhHdPMzNXRKS4h50CH0M5ombwPQQFTB6QPQoU-pyE_JH0aMeVHkYx65MS5JaUUQIbHpMchiDhQ2SezyfT78wuCsWfyKrOpRedhZVcLzKzJPFukmclzs7Jl0T7eoslN4VWurK1x1nmmSDyzKisbexh_YG5OyVFqModnuz0gz3e3T-MHfzq7n4yvp34slFC-YCGKhEvFaGDEXFIFIQgUIUgJEY0hCSRGEWMcWcplomLBAZCpMFVtaPiA-J3XrbFq5rqqbW7qjS6N1bvotb1Qi0AyoC1_2fFVXb416FY6ty7GLDMFlo3TjDMaBjwQW_SqQ-O6dK7GdC8Hqrd967Zv_dt3y17stM08x2RP_hXcAqMOWNsMN_-b9OPNS6f8AYRoiNw</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Lauffer, F.</creator><creator>Jargosch, M.</creator><creator>Baghin, V.</creator><creator>Krause, L.</creator><creator>Kempf, W.</creator><creator>Absmaier‐Kijak, M.</creator><creator>Morelli, M.</creator><creator>Madonna, S.</creator><creator>Marsais, F.</creator><creator>Lepescheux, L.</creator><creator>Albanesi, C.</creator><creator>Müller, N.S.</creator><creator>Theis, F.J.</creator><creator>Schmidt‐Weber, C.</creator><creator>Eyerich, S.</creator><creator>Biedermann, T.</creator><creator>Vandeghinste, N.</creator><creator>Steidl, S.</creator><creator>Eyerich, K.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>202004</creationdate><title>IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema</title><author>Lauffer, F. ; Jargosch, M. ; Baghin, V. ; Krause, L. ; Kempf, W. ; Absmaier‐Kijak, M. ; Morelli, M. ; Madonna, S. ; Marsais, F. ; Lepescheux, L. ; Albanesi, C. ; Müller, N.S. ; Theis, F.J. ; Schmidt‐Weber, C. ; Eyerich, S. ; Biedermann, T. ; Vandeghinste, N. ; Steidl, S. ; Eyerich, K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4646-428e4d356207a4b5061814e48155190c1d75e99223e2f35d6c4311e268f6223a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Cell Movement</topic><topic>Dermatitis, Atopic - immunology</topic><topic>Disease Models, Animal</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Inflammation - immunology</topic><topic>Interleukin-17 - immunology</topic><topic>Keratinocytes - immunology</topic><topic>Mice</topic><topic>Neutrophils - immunology</topic><topic>Psoriasis - immunology</topic><topic>Th17 Cells - immunology</topic><topic>Th2 Cells - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lauffer, F.</creatorcontrib><creatorcontrib>Jargosch, M.</creatorcontrib><creatorcontrib>Baghin, V.</creatorcontrib><creatorcontrib>Krause, L.</creatorcontrib><creatorcontrib>Kempf, W.</creatorcontrib><creatorcontrib>Absmaier‐Kijak, M.</creatorcontrib><creatorcontrib>Morelli, M.</creatorcontrib><creatorcontrib>Madonna, S.</creatorcontrib><creatorcontrib>Marsais, F.</creatorcontrib><creatorcontrib>Lepescheux, L.</creatorcontrib><creatorcontrib>Albanesi, C.</creatorcontrib><creatorcontrib>Müller, N.S.</creatorcontrib><creatorcontrib>Theis, F.J.</creatorcontrib><creatorcontrib>Schmidt‐Weber, C.</creatorcontrib><creatorcontrib>Eyerich, S.</creatorcontrib><creatorcontrib>Biedermann, T.</creatorcontrib><creatorcontrib>Vandeghinste, N.</creatorcontrib><creatorcontrib>Steidl, S.</creatorcontrib><creatorcontrib>Eyerich, K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lauffer, F.</au><au>Jargosch, M.</au><au>Baghin, V.</au><au>Krause, L.</au><au>Kempf, W.</au><au>Absmaier‐Kijak, M.</au><au>Morelli, M.</au><au>Madonna, S.</au><au>Marsais, F.</au><au>Lepescheux, L.</au><au>Albanesi, C.</au><au>Müller, N.S.</au><au>Theis, F.J.</au><au>Schmidt‐Weber, C.</au><au>Eyerich, S.</au><au>Biedermann, T.</au><au>Vandeghinste, N.</au><au>Steidl, S.</au><au>Eyerich, K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema</atitle><jtitle>JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY</jtitle><addtitle>J Eur Acad Dermatol Venereol</addtitle><date>2020-04</date><risdate>2020</risdate><volume>34</volume><issue>4</issue><spage>800</spage><epage>809</epage><pages>800-809</pages><issn>0926-9959</issn><eissn>1468-3083</eissn><abstract>Background
Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear.
Objective
We sought to characterize the role of IL‐17C in human ISD.
Methods
IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined.
Results
Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo.
Conclusion
IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.</abstract><cop>England</cop><pmid>31793105</pmid><doi>10.1111/jdv.16126</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Animals Cell Movement Dermatitis, Atopic - immunology Disease Models, Animal Gene Expression Humans Inflammation - immunology Interleukin-17 - immunology Keratinocytes - immunology Mice Neutrophils - immunology Psoriasis - immunology Th17 Cells - immunology Th2 Cells - immunology |
| title | IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema |
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