Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway
<p dir="ltr">Rosacea is a chronic inflammatory disease of facial skin with unknown pathophysiology. Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea. However, its significance in the rosacea pathogenesis is not fully understood. We sought to under...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2025
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513539930062848 |
|---|---|
| author | Abdul W. Ansari (14557391) |
| author2 | Tanwir Habib (47644) Fareed Ahmad (134672) Thesni Raheed (17017779) Cynthia Elizabeth (14152452) Sara Al-Harami (22150180) Anh Jochebeth (17017782) Martin Steinhoff (5340194) |
| author2_role | author author author author author author author |
| author_facet | Abdul W. Ansari (14557391) Tanwir Habib (47644) Fareed Ahmad (134672) Thesni Raheed (17017779) Cynthia Elizabeth (14152452) Sara Al-Harami (22150180) Anh Jochebeth (17017782) Martin Steinhoff (5340194) |
| author_role | author |
| dc.creator.none.fl_str_mv | Abdul W. Ansari (14557391) Tanwir Habib (47644) Fareed Ahmad (134672) Thesni Raheed (17017779) Cynthia Elizabeth (14152452) Sara Al-Harami (22150180) Anh Jochebeth (17017782) Martin Steinhoff (5340194) |
| dc.date.none.fl_str_mv | 2025-08-18T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.jid.2025.08.003 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Cathelicidin_LL-37-induced_transcriptome_of_human_keratinocyte_identifies_chemokine_CXCL10_link_to_T_cell-mediated_rosacea_pathogenesis_via_JAK-1_STAT-1_pathway/30018739 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Immunology Rosacea Pathophysiology LL-37 CXCL10 T cell |
| dc.title.none.fl_str_mv | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Rosacea is a chronic inflammatory disease of facial skin with unknown pathophysiology. Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea. However, its significance in the rosacea pathogenesis is not fully understood. We sought to understand the molecular mechanisms of LL-37-mediated rosacea-like inflammation in an in-vitro model of normal human epidermal keratinocytes. Transcriptome profiling of LL-37-treated keratinocytes identified signatures of interferon (IFN)-stimulating genes (ISGs) such as<i> CXCL10, IFIT2, RSAD2 </i>and<i> CXCL11</i> among the top upregulated differentially expressed genes. Gene ontogeny (GO) enrichment of biological processes revealed activation of cellular response to molecules of bacterial origin, response to chemokines, and cytokine mediated signaling pathways. While KEGG enrichment analysis revealed the activation of TNF signaling, IL-17 signaling, NF-kB signaling and chemokine signaling among the most significant pathways. Remarkably, T cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure. Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway. In summary, our findings provide a crucial link to keratinocyte: T cell crosstalk and blockade of CXCL10:CXCR3 axis or JAK-1/STAT-1 pathways can be an effective anti-inflammatory strategy to reduce rosacea inflammation by restricting pathogenic T cells infiltration.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Investigative Dermatology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jid.2025.08.003" target="_blank">https://dx.doi.org/10.1016/j.jid.2025.08.003</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d9d4eb51b33b5fe0f4db275056a0585a |
| identifier_str_mv | 10.1016/j.jid.2025.08.003 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30018739 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathwayAbdul W. Ansari (14557391)Tanwir Habib (47644)Fareed Ahmad (134672)Thesni Raheed (17017779)Cynthia Elizabeth (14152452)Sara Al-Harami (22150180)Anh Jochebeth (17017782)Martin Steinhoff (5340194)Biomedical and clinical sciencesClinical sciencesImmunologyRosaceaPathophysiologyLL-37CXCL10T cell<p dir="ltr">Rosacea is a chronic inflammatory disease of facial skin with unknown pathophysiology. Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea. However, its significance in the rosacea pathogenesis is not fully understood. We sought to understand the molecular mechanisms of LL-37-mediated rosacea-like inflammation in an in-vitro model of normal human epidermal keratinocytes. Transcriptome profiling of LL-37-treated keratinocytes identified signatures of interferon (IFN)-stimulating genes (ISGs) such as<i> CXCL10, IFIT2, RSAD2 </i>and<i> CXCL11</i> among the top upregulated differentially expressed genes. Gene ontogeny (GO) enrichment of biological processes revealed activation of cellular response to molecules of bacterial origin, response to chemokines, and cytokine mediated signaling pathways. While KEGG enrichment analysis revealed the activation of TNF signaling, IL-17 signaling, NF-kB signaling and chemokine signaling among the most significant pathways. Remarkably, T cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure. Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway. In summary, our findings provide a crucial link to keratinocyte: T cell crosstalk and blockade of CXCL10:CXCR3 axis or JAK-1/STAT-1 pathways can be an effective anti-inflammatory strategy to reduce rosacea inflammation by restricting pathogenic T cells infiltration.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Investigative Dermatology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jid.2025.08.003" target="_blank">https://dx.doi.org/10.1016/j.jid.2025.08.003</a></p>2025-08-18T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.jid.2025.08.003https://figshare.com/articles/journal_contribution/Cathelicidin_LL-37-induced_transcriptome_of_human_keratinocyte_identifies_chemokine_CXCL10_link_to_T_cell-mediated_rosacea_pathogenesis_via_JAK-1_STAT-1_pathway/30018739CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/300187392025-08-18T09:00:00Z |
| spellingShingle | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway Abdul W. Ansari (14557391) Biomedical and clinical sciences Clinical sciences Immunology Rosacea Pathophysiology LL-37 CXCL10 T cell |
| status_str | publishedVersion |
| title | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| title_full | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| title_fullStr | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| title_full_unstemmed | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| title_short | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| title_sort | Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway |
| topic | Biomedical and clinical sciences Clinical sciences Immunology Rosacea Pathophysiology LL-37 CXCL10 T cell |