d8f60261e93af53fee63726a5584de39 pmc_9570367.pdf af823b2fff4213e0780fe5e1744a26ee7e7d88a0 pmc_9570367.pdf adf5651f2e42e7d0e1f1239d0eeae142d03031821846b1337e4fa36fd7ce7ed7 pmc_9570367.pdf Title: Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn’s Disease Subject: Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn’s disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD. Keywords: adipose tissue; infliximab; adalimumab; TNF; creeping fat Author: Albert Boronat-Toscano, Diandra Monfort-Ferré, Margarita Menacho, Aleidis Caro, Ramon Bosch, Beatriz Espina, Francisco Algaba-Chueca, Alfonso Saera-Vila, Alicia Moliné, Marc Marti, Eloy Espin, Mónica Millan and Carolina Serena Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Sep 22 14:45:00 2022 CEST ModDate: Thu Sep 22 14:52:27 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2604138 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZTKRIF+VnURWPalladioL Type 1 Custom yes yes no 10 0 DKIQIG+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ZWCZVD+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 UPQJXL+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Adipose Tissue Is Remodeled by Anti-TNF Therapy, Which Restores Adipocyte Morphology and Suppresses Immune Cell Infiltration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Anti-TNF Therapies Influence the Creeping Fat, Reducing Inflammation in Various Cell Subtypes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Anti-TNF Treatments Promote a Pro-Inflammatory-to-Anti-Inflammatory Phenotypic Switch in Adipose-Stem Cells Isolated from the Creeping Fat of Patients with Crohn’s Disease Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Histological Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Haematoxylin and Eosin Staining Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: CD68 and Double CD68-CD3 Immunohistochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Isolation and Culture of Adipose Tissue-Derived Stem Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Adipose Stem Cell Immunophenotyping Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Isolation and Incubation of Adipose Tissue Explants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: RNA Extraction and Real-Time Quantitative PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Western Blotting Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Cytokine Secretion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Proteomics Analysis of Conditioned Medium from Adipose-Derived Stem Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Antigen-Presentation Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn’s Disease Author: Albert Boronat-Toscano, Diandra Monfort-Ferré, Margarita Menacho, Aleidis Caro, Ramon Bosch, Beatriz Espina, Francisco Algaba-Chueca, Alfonso Saera-Vila, Alicia Moliné, Marc Marti, Eloy Espin, Mónica Millan and Carolina Serena Subject: Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn’s disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD. 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