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. Winzer R, Hiefner J, Hackbusch R, Link MA, Thomalla G, Tolosa E, Worthmann A. Reliable Determination of ATP and Its Metabolites by LC-MS Using Blood Collection Tubes with and without Ectonucleotidase Inhibitors. ACS Pharmacol Transl Sci. 2025 Nov 7;8(12):4326-4334.
2. Walzik D, Joisten N, Schenk A, Trebing S, Schaaf K, Metcalfe AJ, Spiliopoulou P, Hiefner J, McCann A, Watzl C, Ueland PM, Gehlert S, Worthmann A, Brenner C, Zimmer P. Acute exercise boosts NAD+ metabolism of human peripheral blood mononuclear cells. Brain Behav Immun. 2025 Jan;123:1011-1023
3. Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong MN, Kylies D, Gräfe SK, Edenhofer I, Aranda-Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm AB, Richardt U, Eggert P, Tappe D, Weidemann SA, Ghosh S, Krebs CF, A-Gonzalez N, Worthmann A, Lohse AW, Huber S, Rothlin CV, Puelles VG, Jacobs T, Gagliani N, Bosurgi L. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science. 2024 Apr 5;384(6691):eabo7027.
4. Worthmann A, Ridder J, Piel SYL, Evangelakos I, Musfeldt M, Voß H, O'Farrell M, Fischer AW, Adak S, Sundd M, Siffeti H, Haumann F, Kloth K, Bierhals T, Heine M, Pertzborn P, Pauly M, Scholz JJ, Kundu S, Fuh MM, Neu A, Tödter K, Hempel M, Knippschild U, Semenkovich CF, Schlüter H, Heeren J, Scheja L, Kubisch C, Schlein C. Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use. Nat Commun. 2024 Jan 2;15(1):45.
5. Hiefner J, Rische J, Bunders MJ, Worthmann A. A liquid chromatography-tandem mass spectrometry based method for the quantification of adenosine nucleotides and NAD precursors and products in various biological samples. Front Immunol. 2023 Sep 20;14:1250762.
6. Siracusa F, Schaltenberg N, Kumar Y, Lesker TR, Steglich B, Liwinski T, Cortesi F, Frommann L, Diercks BP, Bönisch F, Fischer AW, Scognamiglio P, Pauly MJ, Casar C, Cohen Y, Pelczar P, Agalioti T, Delfs F, Worthmann A, Wahib R, Jagemann B, Mittrücker HW, Kretz O, Guse AH, Izbicki JR, Lassen KG, Strowig T, Schweizer M, Villablanca EJ, Elinav E, Huber S, Heeren J, Gagliani N. Short-term dietary changes can result in mucosal and systemic immune depression. Nat Immunol. 2023 Sep;24(9):1473-1486.
7. Liebold I, Meyer S, Heine M, Kuhl A, Witt J, Eissing L, Fischer AW, Koop AC, Kluwe J, Wiesch JSZ, Wehmeyer M, Knippschild U, Scheja L, Heeren J, Bosurgi L*, Worthmann A*. TREM2 Regulates the Removal of Apoptotic Cells and Inflammatory Processes during the Progression of NAFLD. Cells. 2023 Jan 17;12(3):341.
8. Rohde JK, Fuh MM, Evangelakos I, Pauly MJ, Schaltenberg N, Siracusa F, Gagliani N, Tödter K, Heeren J, Worthmann A. A Gas Chromatography Mass Spectrometry-Based Method for the Quantification of Short Chain Fatty Acids. Metabolites. 2022 Feb 11;12(2):170. 
9. 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
10. 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.

Prof. Dr. Madeleine Bunders

Selected publications

 

1. Skenteris NT, Luttermann E, Nair S, Evangelakos I, Pujantell M, Eggers M, Hausmann F, Bérouti M, Padoan B, Flomm FJ, Claussen JM, Grünhagel B, Salfelder A, Beifuss B, Biskup S, Blümke P, Rading K, Hildebrandt H, Matschl U, Giesemann-Jansen S, Hennesen J, Nikolaev VO, Kutsche M, Kubisch C, Koch-Nolte F, Tomas NM, Tolosa E, Lütgehetmann M, Stahl FR, Hornung V, Bunders MJ, Schlein C, Topf M, Kötter I, Altfeld M. Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome. JCI Insight. 2026 Feb 23;11(4):e187422.
2. Mataramvura H, Jordan-Paiz A, Naidoo K, Jaeger J, Testa L, Gumbo FZ, Mazengera RL, Bunders MJ, Duri K. Altered mitochondrial mass and fatty acid uptake by natural killer cells in HIV-exposed uninfected children at 6 years of age. AIDS. 2025 Sep 1;39(11):1505-1517.
3. Schuppert P, Pagerols Raluy L, Trochimiuk M, Li Z, Bunders MJ, Reinshagen K, Tomuschat C. Exploring cell death mechanisms in spheroid cultures using a novel application of the RIP3-caspase3-assay. Sci Rep. 2024 Jul 11;14(1):16032. 
4. Padoan B, Casar C, Krause J, Schultheiss C, Baumdick ME, Niehrs A, Zecher BF, Pujantell M, Yuki Y, Martin M, Remmerswaal EBM, Dekker T, van der Bom-Baylon ND, Noble JA, Carrington M, Bemelman FJ, van Lier RAW, Binder M, Gagliani N, Bunders MJ, Altfeld M. NKp44/HLA-DP-dependent regulation of CD8 effector T cells by NK cells. Cell Rep. 2024 Apr 23;43(4):114089.
5. Baumdick ME, Niehrs A, Degenhardt F, Schwerk M, Hinrichs O, Jordan-Paiz A, Padoan B, Wegner LHM, Schloer S, Zecher BF, Malsy J, Joshi VR, Illig C, Schröder-Schwarz J, Möller KJ; Hamburg Intestinal Tissue Study Group; Martin MP, Yuki Y, Ozawa M, Sauter J, Schmidt AH, Perez D, Giannou AD, Carrington M, Davis RS, Schumacher U, Sauter G, Huber S, Puelles VG, Melling N, Franke A; International Inflammatory Bowel Disease Genetics Consortium; Altfeld M*, Bunders MJ*. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44⁺Natural Killer Cells in Ulcerative Colitis. Gastroenterology. 2023 Oct;165(4):946-962.e13. 
6. Hiefner J, Rische J, Bunders MJ, Worthmann A. A liquid chromatography-tandem mass spectrometry based method for the quantification of adenosine nucleotides and NAD precursors and products in various biological samples. Front Immunol. 2023 Sep 20;14:1250762.
7. Möller KJ, Wegner LHM, Malsy J, Baumdick ME, Borggrewe M, Jordan-Paiz A, Jung JM, Martrus G, Kretschmer P, Sagebiel AF, Schreurs RRCE, Hagen SH, Burmester G, Clauditz TS, Pals ST, Boettcher M, Melling N, Sauter G, Tomuschat C, Königs I, Schumacher U, Altfeld M, Bernink JH, Perez D, Reinshagen K, Bunders MJ. Expanded ILC2s in human infant intestines promote tissue growth. Mucosal Immunol. 2023 Aug;16(4):408-421.
8. 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.
9. 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
10. 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

Our Team