{"title":"IL-34 is expressed in the pancreas and regulates local inflammation","authors":"Chloé M Delépine , Emilie Courty , Laurence Preisser , Raffaella Soleti , Laetitia Basset , Audrey Le Guernic , Laure Rolland , Marine Monnier , Gianni Pasquetti , Simon Blanchard , Pascale Pignon , Nathalie Merillon , Julie Kerr-Conte , Charline Miot , Dominique Couez , Aline Schmidt-Tanguy , Elise Dalmas , Pascale Jeannin , Jean-Sébastien Annicotte , Yves Delneste , Celine Beauvillain","doi":"10.1016/j.trsl.2025.07.002","DOIUrl":"10.1016/j.trsl.2025.07.002","url":null,"abstract":"<div><div>Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of <em>Il34</em> in mice (IL-34<sup>ΔPdx</sup>) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34<sup>ΔPdx</sup> mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, <em>ex vivo</em> murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of <em>Il-34</em> mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 56-67"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rubén Osuna-Gómez , Ivan Castellví , Maria Mulet , Jose Luis Tandaipan , Carlos Zamora , Helena Codes-Mendez , Mª Àngels Ortiz , Cesar Diaz-Torné , Elisabet Cantó , Berta Magallares , Albert Guinart-Cuadra , Patricia Moya , Hector Corominas , Silvia Vidal
{"title":"Platelet bound B cells and their role in SSc: Implications for disease subtypes and clinical outcomes","authors":"Rubén Osuna-Gómez , Ivan Castellví , Maria Mulet , Jose Luis Tandaipan , Carlos Zamora , Helena Codes-Mendez , Mª Àngels Ortiz , Cesar Diaz-Torné , Elisabet Cantó , Berta Magallares , Albert Guinart-Cuadra , Patricia Moya , Hector Corominas , Silvia Vidal","doi":"10.1016/j.trsl.2025.07.001","DOIUrl":"10.1016/j.trsl.2025.07.001","url":null,"abstract":"<div><h3>Objectives</h3><div>Systemic sclerosis (SSc) is a complex autoimmune disease characterized by microvascular damage, immune dysregulation, and tissue fibrosis. While lymphocyte-platelet (PLT) complexes have been implicated in autoimmune diseases, their role in SSc is not well understood. Methods: In a study of 21 predominantly female SSc patients, 66.7 % had limited SSc (lcSSc), with anti-centromere antibodies (ACA) being the most common autoantibody pattern. We applied flow cytometry to analyze B cells with bound PLTs, enzyme-linked immunosorbent assay (ELISA) to determine plasma levels of activated PLT soluble factors, and co-culture assays to evaluate B cell cytokine secretion and plasma cell differentiation. Results: SSc patients had a higher percentage of B cells, but not T cells, with bound PLTs compared to healthy donors (HD). Despite similar PLT counts, SSc patients showed higher plasmatic levels of P-selectin (CD62P), soluble CD40 ligand (sCD40L), platelet-derived growth factor (PDGF), and transforming growth factor–β (TGF-β). Plasma IL-10 levels were also higher in SSc patients, with increased intracellular IL-10 in B cells with bound PLTs. We observed an increased IL-10 production and plasma cell differentiation when B cells were co-cultured with PLTs, especially from SSc patients. B cells with bound PLTs were associated with calcinosis, digital ulcers, and ACA status, with no effect from previous corticosteroid or aspirin therapy. Logistic regression identified B cells with bound PLTs as a predictor for distinguishing lcSSc patients. Conclusions: B cells with bound PLTs play a significant role in SSc by modulating B cell function and contributing to disease pathogenesis. Their association with clinical parameters suggests their potential as biomarkers for disease severity and subtype classification in SSc.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 31-40"},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cai Gao , Jinzhao He , Yiming Wang , Guangying Shao , Simei Lin , Jihan Liu , Chaoqun Ren , Yazhu Quan , Yi Ying , Min Li , Baoxue Yang , Hong Zhou
{"title":"The role of FAK in renal collecting duct in the progression from acute kidney injury to chronic kidney disease","authors":"Cai Gao , Jinzhao He , Yiming Wang , Guangying Shao , Simei Lin , Jihan Liu , Chaoqun Ren , Yazhu Quan , Yi Ying , Min Li , Baoxue Yang , Hong Zhou","doi":"10.1016/j.trsl.2025.06.002","DOIUrl":"10.1016/j.trsl.2025.06.002","url":null,"abstract":"<div><div>AKI and CKD are major global health problem, which closely connected and promote each other. The mechanism may be related to maladaptive repair after renal tubular injury. FAK is a non-receptor tyrosine kinase located at the intersection of multiple cell signal transduction pathways. Previous studies have suggested that FAK may be involved in the repair process after kidney injury, but its role and mechanism in the process of AKI to CKD need to be further elucidated. In this study, we found that FAK was up-regulated in AKI to CKD and mainly localized in renal collecting ducts. Therefore, we generated renal collecting duct specific FAK knockout mice, which were treated with RIRI and UUO models to simulate the progression of AKI and CKD. This study for the first time found that the specific knockout of FAK in renal collecting duct can reduce oxidative stress and inflammatory response in the early stage of kidney injury, improve renal function, inhibit renal fibrosis, and significantly prolong the survival time of mice. In terms of mechanism, FAK knockout in renal collecting duct may affect inflammatory cell infiltration through KLF5 signaling pathway, regulate the trend of adaptive repair and maladaptive repair of renal tubular cells after injury, and promote the damaged kidney tubules restore health. Therefore, this study confirmed that loss of FAK function in the renal collecting duct can delay the progression of AKI to CKD by inhibiting inflammation-regulated maladaptive kidney repair, which providing a novel potential strategy for the clinical treatment of AKI to CKD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 41-55"},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eun Na Kim , Hee Young Seok , Jiwon Koh , Jeong Mo Bae , Wookyeom Yang , Gyu Ho Lee , Woo Hee Choi , Joon Seo Lim , You Jung Ok , Jae-Sung Choi , Donghee Kim , Chong Jai Kim , Lizhe Zhuang , Young Hwan Chang , Se Jin Oh
{"title":"Multiplexed imaging-driven single-cell analysis of abdominal aortic aneurysm according to C-reactive protein deposition","authors":"Eun Na Kim , Hee Young Seok , Jiwon Koh , Jeong Mo Bae , Wookyeom Yang , Gyu Ho Lee , Woo Hee Choi , Joon Seo Lim , You Jung Ok , Jae-Sung Choi , Donghee Kim , Chong Jai Kim , Lizhe Zhuang , Young Hwan Chang , Se Jin Oh","doi":"10.1016/j.trsl.2025.05.008","DOIUrl":"10.1016/j.trsl.2025.05.008","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) is an age-related, life-threatening condition characterized by the expansion of the abdominal aorta. Serum C-reactive protein (CRP) levels are a prognostic marker for AAA, and CRP accelerates tissue injury when deposited in damaged cell membranes in its monomeric form (mCRP). We previously showed that mCRP deposits in eroded atherosclerotic regions are associated with increases in inflammatory cell infiltration and aortic diameter. To investigate the changes in inflammatory-stromal cellular landscape associated with mCRP deposition, we used Co-Detection by Indexing (CODEX) tissue imaging with 31 nucleotide-barcoded antibodies and single-cell-based unsupervised clustering. AAA cases were categorized into High-CRP (<em>n</em> = 6) and Low-CRP (<em>n</em> = 3) groups based on serum levels and immunohistochemistry scores of mCRP. We identified 47 distinct immune and stromal cell types, revealing significant differences in protein expression between groups. In AAA, stromal cells decreased while immune cells increased. High-CRP cases showed increased M1-like and Ki67<sup>+</sup> proliferating macrophages, and reduced αSMA<sup>+</sup> cells, whereas Low-CRP cases exhibited intensified fibrosis with CD163<sup>+</sup>Ki67<sup>+</sup> proliferating M2-like macrophages. Spatial neighborhood enrichment analysis highlighted the close proximity of CD4<sup>+</sup>FOXP3<sup>+</sup>PDL1<sup>+</sup> T<sub>reg</sub> cells to specific clusters: (1) CD57<sup>+</sup>granzyme <em>B</em><sup>+</sup> cytotoxic NK cells, (2) CD31<sup>+</sup>HLA-<em>A</em><sup>+</sup> endothelial cells, (3) CD45<sup>+</sup>lymphocytes/CD31<sup>+</sup> endothelial cells, and (4) CD45<sup>+</sup>CD20<sup>+</sup> <em>B</em> cells in High-CRP cases. Our findings demonstrate the varying distribution of immune cells and vascular wall phenotypes in AAA according to mCRP deposition levels. Targeting inflammation, specifically the immune cells, macrophages, and fibrosis affected by mCRP, may represent a novel approach to halting the pathogenesis of AAA.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 14-30"},"PeriodicalIF":6.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}