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. 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.

2. 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.

3. 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.

4. 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.

5. 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. 

6. 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.

7. 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.

8. 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

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. 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.

2. 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. 

3. 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.

4. Lücke J, Heinrich F, Malsy J, Meins N, Schnell J, Böttcher M, Nawrocki M, Zhang T, Bertram F, Sabihi M, Kempski J, Blankenburg T, Duprée A, Reeh M, Wolter S, Mann O, Izbicki JR, Lohse AW, Gagliani N, Lütgehetmann M, Bunders MJ, Altfeld M, Sauter G, Giannou AD, Krasemann S, Ondruschka B, Huber S. Intestinal IL-1β Plays a Role in Protecting against SARS-CoV-2 Infection. J Immunol. 2023 Sep 15;211(6):1052-1061.

5. 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.

6. Zhang Z, Duri K, Duisters KLW, Schoeman JC, Chandiwana P, Lindenburg P, Jaeger J, Ziegler S, Altfeld M, Kohler I, Harms A, Gumbo FZ, Hankemeier T, Bunders MJ. Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children. AIDS. 2023 Jul 15;37(9):1367-1376.

7. Jordan-Paiz A, Martrus G, Steinert FL, Kaufmann M, Sagebiel AF, Schreurs RRCE, Rechtien A, Baumdick ME, Jung JM, Möller KJ, Wegner L, Grüttner C, Richert L, Thünauer R, Schroeder-Schwarz J, van Goudoever JB, Geijtenbeek TBH, Altfeld M, Pals ST, Perez D, Klarenbeek PL, Tomuschat C, Sauter G, Königs I, Schumacher U, Friese MA, Melling N, Reinshagen K, Bunders MJ. CXCR5⁺PD-1⁺⁺ CD4⁺ T cells colonize infant intestines early in life and promote B cell maturation. Cell Mol Immunol. 2023 Feb;20(2):201-213.

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