The Wensveen Lab
Great work of first author Karlo Mladenić and the rest of the team for publishing a great Review article on the mechanisms of inflammation in fatty liver disease in the European Journal of Immunology.
Read the article here:
Read our latest manuscript on the first steps of hepatic inflammation in context of fatty liver disease in Science Immunology!
Read the article here:
Assoc.Prof. Felix Wensveen
Specialists on immuno-endocrinology and anti-viral immunology
Since 2006, the focus of my research has been on how lymphocytes deal with cellular stress, such as infections, but also metabolic stress. People can be infected with a shockingly large number of pathogens such as bacteria and viruses. In addition, cells can malfunction due to oncogenic transformation or as a result of the accumulation of metabolites in context of obesity. Somehow, the immune system must be able to identify all these signals as a reason to respond, whilst leaving all the molecular structures healthy tissues intact. Once the threat has been eliminated, the immune system must retain a small but effective, standing army in the form of memory cells, that protect from re-infection with the original pathogen, but also of potential mutants.
All of these examples require complex molecular strategies which we are studying in my group. More recently, we have expanded our research to investigate not only how the immune system directly identifies and eliminates these threats, but also how it modifies systemic metabolism in order to optimally fight incursions. Our work has identified several mechanisms how this system derails in the context of metabolic disease.
Research highlights:
Mladenić K, Lenartić M, Marinović S, Polić B, Wensveen FM, The “Domino effect” in MASLD: The Inflammatory cascade of steatohepatitis Eur J Immunol. 2024 accepted for publication.
Gašparini D, Wensveen FM, Turk Wensveen T. Inflammageing mediated by cytotoxic lymphocytes is associated with diabetes duration Diabetes Res Clin Pract. 2023 Dec 15:207:111056. doi: 10.1016/j.diabres.2023.111056.
Gašparini D, Zuljani A, Wensveen FM, Turk Wensveen T., A cross-sectional study in type 2 diabetes patients reveals that elevated pulse wave velocity predicts asymptomatic peripheral arterial disease associated with age and diabetes duration. Int J Cardiol Heart Vasc. 2023 Nov 26;49:101308. doi: 10.1016/j.ijcha.2023.101308
Marinović S, Lenartić M, Mladenić K , Šestan, M, Kavazović I, Benić A, Krapić M, Rindlisbacher L, Cokarić Brdovčak M, Sparano C, Litscher G, Turk Wensveen T, Mikolasevic I, Fučkar Čupić D, Bilić-Zulle L, Steinle A, Waisman A, Hayday A, Tugues S, Becher B, Polić B, Wensveen FM, NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis, Sci Immunol. 2023 Sep 29;8(87):eadd1599. doi: 10.1126/sciimmunol.add1599.
Imširović V, Lenartić M, Wensveen FM, Polić B, Jelenčić V. Largely preserved functionality after the combined loss of NKG2D, NCR1 and CD16 demonstrates the remarkable plasticity of NK cell responsiveness. Front Immunol. 2023 Jul 13;14:1191884. doi: 10.3389/fimmu.2023.1191884. eCollection 2023.
Kavazović I, Dimitropoulos C, Gašparini D, Rončević Filipović M, Barković I, Koster J, Lemmermann NA, Babić M, Cekinović Grbeša Đ, Wensveen FM.,, Vaccination provides superior in vivo recall capacity of SARS-CoV-2-specific memory CD8 T cells. Cell Rep. 2023 Apr 4;42(4):112395. doi: 10.1016/j.celrep.2023.112395.
Martens AWJ, Kavazović I, Krapić M, Pack SM, Arens R, Jongejan A, Moerland PD, Eldering E, van der Windt GJW, Wensveen FM, Peters FS, Kater AP. Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors. Leukemia. 2023 Jan 19:1-11. doi: 10.1038/s41375-023-01817-z.
Benić A, Mikašinović S, Wensveen FM, Polić B, Activation of Granulocytes in Response to a High Protein Diet Leads to the Formation of Necrotic Lesions in the Liver. Metabolites, 13 (2023), 2; 153. https://doi.org/10.3390/metabo13020153
Gašparini D, Kavazović I, Barković I, Maričić V, Ivaniš V, Samsa DT, Peršić V, Polić B, Turk Wensveen T, Wensveen FM. Extreme anaerobic exercse causes reduced cytotoxicity and increased cytokine production by peripheral blood lymphocytes. Immunol Lett. 2022 Aug;248:45-55. doi: 10.1016/j.imlet.2022.06.001. Epub 2022 Jun 13.
Kavazović I, Krapić M, Beumer-Chuwonpad A, Polić B, Turk Wensveen T, Lemmermann NA, Van Gisbergen KPJM, Wensveen FM, Hyperglycemia and not hyperinsulinemia mediates diabetes-induced memory CD8 t cell dysfunction, Diabetes. 2022. Apr 1;71(4):706-721. doi: 10.2337/db21-0209.
Krapić M, Kavazović I, Wensveen FM. Immunological Mechanisms of Sickness Behavior in Viral Infection. Viruses. 2021 Nov 8;13(11):2245. doi: 10.3390/v13112245.
Parga-Vidal L, Behr FM, Kragten NAM, Nota B, Wesselink TH, Kavazović I, Covill LE, Schuller MBP, Bryceson YT, Wensveen FM, van Lier RAW, van Dam TJP, Stark R, van Gisbergen KPJM. Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes. Sci Immunol. 2021 Aug 20;6(62):eabg3533. doi: 10.1126/sciimmunol.abg3533.
Wensveen FM, Šestan M, Turk Wensveen T, Polić B. Blood glucose regulation in context of infection. Vitam Horm. 2021;117:253-318. doi: 10.1016/bs.vh.2021.06.009.
Turk Wensveen T, Gašparini D, Rahelić D, Wensveen FM, Type 2 diabetes and viral infection; cause and effect of disease. Diabetes Res Clin Pract. 2021 Feb;172:108637.
Kavazović I, Han H, Balzaretti G, Slinger E, Lemmermann NAW, Ten Brinke A, Merkler D, Koster J, Bryceson Y, De Vries N, Jonjić S, Klarenbeek PL, Polić B, Eldering E, Wensveen FM, Eomes broadens the scope of CD8 T cell memory by inhibiting apoptosis in cells of low affinity. PLoS Biol. 2020 Mar 17;18(3):e3000648. doi: 10.1371/journal.pbio.3000648.
Turk Wensveen T, Fučkar Ćupić D, Jurišić Eržen D, Polić B, Wensveen FM, Severe lipoatrophy in a patient with diabetes mellitus type 2 in response to glargine and degludec insulin: Possible involvement of CD4 T cell mediated tissue remodelling. Diabetes Care. 2020 Feb;43(2):494-496. doi: 10.2337/dc19-1888.
Šestan M, Marinović S, Kavazović I, Cekinović Đ, Wueest S, Turk Wensveen T, Brizić I, Jonjić S, Konrad D, Wensveen FM, Polić B. Virus-Induced Interferon-γ Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity. Immunity. 2018 Jul 17;49(1):164-177.e6. doi: 10.1016/j.immuni.2018.05.005.
Wensveen FM, Jelenčić V, Valentić S, Šestan M, Wensveen TT, Theurich S, Glasner A, Mendrila D, Štimac D, Wunderlich FT, Brüning JC, Mandelboim O, Polić B. NK cells link obesity-induced adipose stress to inflammation and insulin resistance. Nat Immunol. 2015 Apr;16(4):376-85. doi: 10.1038/ni.3120.
Wensveen FM, Derks IA, van Gisbergen KP, de Bruin AM, Meijers JC, Yigittop H, Nolte MA, Eldering E, van Lier RA. BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation. Blood. 2012 Feb 9;119(6):1440-9. doi: 10.1182/blood-2011-09-378877.
Wensveen FM, van Gisbergen KP, Derks IA, Gerlach C, Schumacher TN, van Lier RA, Eldering E. Apoptosis threshold set by Noxa and Mcl-1 after T cell activation regulates competitive selection of high-affinity clones. Immunity. 2010 Jun 25;32(6):754-65. doi: 10.1016/j.immuni.2010.06.005.
A full list of publications of my group can be found HERE.
Group leader Felix Wensveen won the 2019 award of the Croatian Academy of Sciences and Arts for the best Scientific achievement in the field of Medical Sciences!
http://info.hazu.hr/upload/File/2020/DEPLIJAN-NAGRADE-HAZU-2020-INACICA-03.pdf