{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:13:11Z","timestamp":1793113991285,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> SDF-1\/CXCL12 is a chemokine with pleiotropic functions in hematopoietic stem cell niche homeostasis, germinal center architecture, B cell maturation, neoangiogenesis, and fibrosis. Recently, the CXCL12\/CXCR4\/CXCR7 axis was associated with cancer metastasis and autoimmune diseases. The IgG4-related disease (IgG4-RD) is a pathological condition characterized by IgG4+ plasma cells infiltrating fibrotic lesions. The aim of this research is to investigate the relevance of SDF-1\/CXCL12 in IgG4-RD.<\/jats:p><jats:p><jats:bold>Materials and Methods:<\/jats:bold> Peripheral blood samples were collected before therapy from a single-center cohort of 28 IgG4-RD patients, fulfilling the ACR-EULAR classification criteria. Clinical and serological data were obtained for each patient. In total, 14 healthy donors (NHS), 9 patients with pancreatic ductal adenocarcinoma (PDAC), and 9 with Sjogren syndrome (SSj) were recruited as controls and screened for circulating SDF-1\/CXCL12 by ELISA. Moreover, paraffin-embedded pancreatic biopsies obtained from patients with IgG4-RD (<jats:italic>n<\/jats:italic> = 7), non-autoimmune pancreatitis (<jats:italic>n<\/jats:italic> = 3), PDAC (<jats:italic>n<\/jats:italic> = 5), and control tissues (<jats:italic>n<\/jats:italic> = 4) were analyzed to study the tissue expression and localization of SDF-1\/CXCL12 and one of its receptors, CXCR4, and their potential relation with neutrophil extracellular traps (NETs).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> IgG4-RD patients had higher serum levels of SDF-1\/CXCL12 than normal controls (<jats:italic>p<\/jats:italic> = 0.0137). Cytokine levels did not differ between the IgG4-RD autoimmune pancreatitis (AIP) and retroperitoneal fibrosis nor between the single- and multiple-organ involvement. No correlation was seen with the IgG4-RD Responder Index, IgG4 levels, white blood cells, or inflammatory markers in the serum. When compared to SSj, the IgG4-RD AIP subgroup presents higher amounts of serum SDF-1\/CXCL12 (<jats:italic>p<\/jats:italic> = 0.0275), while no differences are seen in comparison with PDAC. The expression of SDF-1\/CXCL12 in the tissue was significantly higher in the IgG4-RD tissue than the normal pancreas, and the tissue with the high SDF-1\/CXCL12 expression is characterized by the overall inflammatory cell infiltration, fibrosis, and high level of NETs.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Modulating B cell development, neoangiogenesis and fibrosis, and SDF-1\/CXCL12 may play a role in IgG4-RD. The higher levels observed in IgG4-RD, as compared to SSj, which closely mimics the disease, can be related to a different pattern of lesions, with prevalent fibrosis seen in IgG4-RD. Taken together, these findings suggest that drugs acting on the CXCL12\/CXCR4\/CXCR7 axis may affect IgG4-RD.<\/jats:p>","DOI":"10.3389\/fphar.2021.750216","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T05:16:18Z","timestamp":1635225378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["CXCL12\/SDF-1 in IgG4-Related Disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Riccardo","family":"Capecchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Croia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Puxeddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Pratesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cacciato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Campani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Boggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Tavoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Migliorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.4049\/jimmunol.1500971","article-title":"Plasmacytoid Dendritic Cell Activation and IFN-\u03b1 Production Are Prominent Features of Murine Autoimmune Pancreatitis and Human IgG4-Related Autoimmune Pancreatitis","volume":"195","author":"Arai","year":"2015","journal-title":"J. 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