{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:07:34Z","timestamp":1789470454112,"version":"build-2803163510"},"reference-count":0,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by immune dysregulation and fibrosis, with myeloid\u2010derived suppressor cells (MDSCs) emerging as important regulators of immune responses. However, the role of MDSCs in SSc\u2010associated fibrosis and their interactions with other immune cell populations remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood (SSc: N=37, healthy: N=27) and skin biopsies (SSc: N=9, healthy: N=5) were analyzed using flow cytometry and fluorescence microscopy, respectively. Bleomycin\u2010induced mouse models of fibrosis were used to validate findings, including pharmacological disruption of granulocytic MDSC (G\u2010MDSC) activity via Bruton's tyrosine kinase inhibition (ibrutinib). Single\u2010cell RNA sequencing data from SSc and control skin and lung samples (skin: 19 SSc, 20 healthy; lung: 7 SSc, 15 healthy), complemented by spatial transcriptomics analysis of skin (12 SSc, 7 healthy), were integrated to define cellular interactions relevant to disease pathogenesis. Functional studies and bulk RNA sequencing were conducted to dissect the underlying G\u2010MDSC interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      G\u2010MDSCs were significantly enriched in the circulation and skin of SSc patients, correlating with disease severity. Experimental fibrosis revealed enrichment of G\u2010MDSCs, whereas monocytic MDSCs remained stable. Transcriptomic data revealed a strong interaction between MDSCs and type 2 innate lymphoid cells (ILC2s), promoting a pro\u2010fibrotic environment via IL\u201013\u2010driven TGF\u03b2, Arginase1 and CCL24. Functional assays confirmed that G\u2010MDSCs promote\n                      <jats:italic>Tgfb1<\/jats:italic>\n                      expression in ILC2s, further driving tissue fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings explore a so far unknown G\u2010MDSC\u2013ILC2 axis as a driver of fibrosis in SSc. Targeting this interaction may represent a novel therapeutic strategy to mitigate fibrotic disease progression.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70325-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70325","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:04:25Z","timestamp":1788771865000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The synergistic impact of granulocytic myeloid\u2010derived suppressor cells and innate lymphoid cells in systemic sclerosis"],"prefix":"10.1002","author":[{"given":"Stefanie","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario R.","family":"Angeli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2565-2702","authenticated-orcid":false,"given":"Hashem","family":"Mohammadian","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Labinsky","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Department of Internal Medicine 2, Rheumatology and Clinical Immunology, Universit\u00e4tsklinikum W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Raimondo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3476-2481","authenticated-orcid":false,"given":"Richard","family":"Demmler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ariza","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wohlfahrt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Luber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-9361","authenticated-orcid":false,"given":"Yi\u2010Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Hiller Research Center University Hospital D\u00fcsseldorf Heinrich\u2010Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"},{"name":"Clinic for Rheumatology University Hospital D\u00fcsseldorf Heinrich\u2010Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg H.W.","family":"Distler","sequence":"additional","affiliation":[{"name":"Hiller Research Center University Hospital D\u00fcsseldorf Heinrich\u2010Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"},{"name":"Clinic for Rheumatology University Hospital D\u00fcsseldorf Heinrich\u2010Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"B\u00e4uerle","sequence":"additional","affiliation":[{"name":"Institute of Radiology Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Department of Radiology, Johannes\u2010Gutenberg\u2010Universit\u00e4t Mainz and Universit\u00e4tsmedizin Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-9615","authenticated-orcid":false,"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Division of Rheumatology, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rauber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ramming","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina M.","family":"Ramming","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 \u2010 Rheumatology and Immunology, Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Friedrich\u2010Alexander\u2010University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70325","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:52:12Z","timestamp":1789469532000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":0,"alternative-id":["10.1002\/art.70325"],"URL":"https:\/\/doi.org\/10.1002\/art.70325","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"assertion":[{"value":"2025-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.70325"}}