A19

A19: Summary

In Crohn’s disease (CD) highly inflamed intestinal segments are enveloped by hyperplastic, fibrotic ‘creeping fat’ providing direct contact between adipocytes (AC) and mucosal epithelial cells (EC). The processes driving the formation of creeping fat and its role for inflammation are poorly understood and our preliminary data suggest that purinergic signaling pathways are affected. Using 3D in vitro organoid models derived from CD patients and controls we aim to unravel the role of adenine nucleotide release, processing and sensing for the crosstalk between intestinal EC and AC and intestinal inflammation and fibrosis.

Dr. Anna Worthmann

Selected publications (*equal contribution)

 

1. Schaltenberg N, John C, Heine M, Haumann F, Rinninger F, Scheja L, Heeren J, Worthmann A. Endothelial Lipase Is Involved in Cold-Induced High-Density Lipoprotein Turnover and Reverse Cholesterol Transport in Mice. Front Cardiovasc Med. 2021;8:628235.

2. Schlein C, Fischer AW, Sass F, Worthmann A, Todter K, Jaeckstein MY, Behrens J, Lynes MD, Kiebish MA, Narain NR, Bussberg V, Darkwah A, Jespersen NZ, Nielsen S, Scheele C, Schweizer M, Braren I, Bartelt A, Tseng YH, Heeren J, Scheja L. Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution. Cell Reports. 2021;34(2):108624.

3. Fischer AW, Jaeckstein MY, Gottschling K, Heine M, Sass F, Mangels N, Schlein C, Worthmann A, Bruns OT, Yuan Y, Zhu H, Chen O, Ittrich H, Nilsson SK, Stefanicka P, Ukropec J, Balaz M, Dong H, Sun W, Reimer R, Scheja L, Heeren J. Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation. Cell Metab 2021;33:547-564

4. Pauly MJ, Rohde JK, John C, Evangelakos I, Koop AC, Pertzborn P, Tödter K, Scheja L, Heeren J, Worthmann A. Inulin Supplementation Disturbs Hepatic Cholesterol and Bile Acid Metabolism Independent from Housing Temperature. Nutrients. 2020;12(10):3200.

5. Worthmann A, Schlein C, Berbée JFP, Rensen PCN, Heeren J, Bartelt A. Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression. Nutrients 2019;11(2). pii: E463

6. Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O'Loughlin E, Xu Y, Fanek Z, Greco DJ, Smith ST, Tweet G, Humulock Z, Zrzavy T, Conde-Sanroman P, Gacias M, Weng Z, Chen H, Tjon E, Mazaheri F, Hartmann K, Madi A, Ulrich JD, Glatzel M, Worthmann A, Heeren J, Budnik B, Lemere C, Ikezu T, Heppner FL, Litvak V, Holtzman DM, Lassmann H, Weiner HL, Ochando J, Haass C, Butovsky O. The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases. Immunity 2017;47(3):566-581.e9

7. Worthmann A*, John C*, Rühlemann MC, Baguhl M, Heinsen FA, Schaltenberg N, Heine M, Schlein C, Evangelakos I, Mineo C, Fischer M, Dandri M, Kremoser K, Scheja L, Franke A, Shaul PW, Heeren J. Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nature Med 2017;23(7):839-849

8. Bartelt A*, John C*, Schaltenberg N*, Berbée JF*, Worthmann A*, Cherradi ML, Schlein C, Julia Piepenburg J, Boon MR, Rinninger F, Heine M, Toedter K, Niemeier A, Nilsson SK, Fischer M, Wijers SL, van Marken Lichtenbelt W, Scheja L, Rensen PC, Heeren J. Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport. Nature Commun 2017;8:15010.

9. Berbée JF, Boon MR, Khedoe PP, Bartelt A, Schlein C, Worthmann A, Kooijman S, Hoeke G, Mol IM, John C, Jung C, Vazirpanah N, Brouwers LP, Gordts PL, Esko JD, Hiemstra PS, Havekes LM, Scheja L, Heeren J, Rensen PC. Brown fat activation reduces hypercholesterolemia and protects from atherosclerosis development. Nature Commun. 2015;6:6356.

10. John C, Werner P, Worthmann A, Wegner K, Todter K, Scheja L, Rohn S, Heeren J, Fischer M. A Liquid Chromatography-Tandem Mass Spectrometry-Based Method for the Simultaneous Determination of Hydroxy Sterols and Bile Acids. J Chromatogr A 2014;1371:184-95.

Prof. Dr. Madeleine Bunders

Selected publications

 

1. Jung JM, Ching W, Baumdick ME, Hofmann-Sieber H, Bosse JB, Koyro T, Möller KJ, Wegner L, Niehrs A, Russu K, Ohms M, Zhang W, Ehrhardt A, Duisters K, Spierings E, Hölzemer A, Körner C, Jansen SA, Peine S, Königs I, Lütgehetmann M, Perez D, Reinshagen K, Lindemans CA, Altfeld M*, Belderbos M*, Dobner T*, Bunders MJ*. KIR3DS1 directs NK cell-mediated protection against human adenovirus infections. Science Immunology. 2021;6:eabe2942.

2. Schreurs RRCE, Baumdick ME, Drewniak A, Bunders MJ. In vitro co-culture of human intestinal organoids and lamina propria-derived CD4+ T cells. Star Protocols Cell Press. 2021;2:100519.

3. Schreurs RRCE, Sagebiel AF, Steinert FL, Highton AJ, Klarenbeek PL, Drewniak A, Bakx R, The SML, Ribeiro CMS, Perez D, Reinshagen K, Geijtenbeek TBH, van Goudoever JB, Bunders MJ. Intestinal CD8+ T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities. Mucosal Immunology. 2021;12: 605–614.

4. Sagebiel AF, Steinert F, Lunemann S, Körner C, Schreurs RRCE, Altfeld M, Perez D, Reinshagen K, Bunders MJ Tissue-resident Eomes(+) NK cells are the major innate lymphoid cell population in human infant intestine. Nature Commun. 2019; 10:975

5. Schreurs RRCE, Baumdick ME*, Sagebiel AF*, Kaufmann M, Mokry M, Klarenbeek PL, Schaltenberg N, Steinert FL, van Rijn JM, Drewniak A, The SML, Bakx R, Derikx JPM, de Vries N, Corpeleijn WE, Pals ST, Gagliani N, Friese MA, Middendorp S, Nieuwenhuis EES, Reinshagen K, Geijtenbeek TBH, van Goudoever JB, Bunders MJ. Human Fetal TNF-α-Cytokine-Producing CD4(+) Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life. Immunity. 2019; 50:462

6. Schreurs RRCE, Drewniak A, Bakx R, Corpeleijn WE, Geijtenbeek THB, van Goudoever JB, Bunders MJ Quantitative comparison of human intestinal mononuclear leukocyte isolation techniques for flow cytometric analyses. J Immunol Methods. 2017; 445:45

7. Schoeman JC, Moutloatse GP, Harms AC, Vreeken RJ, Scherpbier HJ, Van Leeuwen L, Kuijpers TW, Reinecke CJ, Berger R, Hankemeier T*, Bunders MJ.* Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants. J Infect Dis. 2017; 216:436

8. Cohen S, Innes S, Geelen SP, Wells JC, Smit C, Wolfs TF, van Eck-Smit BL, Kuijpers TW, Reiss P, Scherpbier HJ, Pajkrt D, Bunders MJ. Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts. PLoS One. 2015;. 10:e0120927.

9. Bunders MJ, Frinking O, Scherpbier HJ, van Arnhem LA, van Eck-Smit BL, Kuijpers TW, Zwinderman AH, Reiss P, Pajkrt D. Bone mineral density increases in HIV-infected children treated with long-term combination antiretroviral therapy. Clin Infect Dis. 2013; 56:583.

10. Bunders MJ, van der Loos CM, Klarenbeek PL, van Hamme JL, Boer K, Wilde JCH, de Vries N, van Lier RAW, Kootstra N, Pals ST, Kuijpers TW. Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1. Blood. 2012; 120:4383-90.

Our Team