The Wensveen Lab

My team investigates how CD8 T cells function as part of the physiological system that is our body. All organs in our body collaborate to maintain homeostasis of vital nutrients such as glucose, amino acids and lipids. Homeostasis is regulated through several systems, including the endocrine system which controls the activity of organs and mediates their secretion or absorption of nutrients. The immune system was long considered exempt from endocrine control, since immune cells should be given free reign to use the nutrients they need to protect our body from potentially lethal infection. However, recent insights indicate that also the immune cells are sensitive to endocrine signals. Our group investigates how endocrine hormones such as insulin, adiponectin and IGF-1 control immune cell functionality during homeostasis and upon infection. We are particularly interested in CD8 T cells and NK cells. We study these cells in models of viral infection, mostly using mice. In addition, we study CD8 T cell function using mouse models of metabolic disease, as well as using patient material. Our findings indicate that hormone disbalances, such as observed in diabetes mellitus type 2, are a major cause of immune cell disfunction in these patients. As a result, these patients suffer from more and more severe infections. Our work aims to understand the interactions between the endocrine and immune system, with the ultimate purpose to ameliorate the immunological complications of metabolic disease.

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About me...

Born Dutch, I was trained as a T cell immunologist at the University of Amsterdam in The Netherlands in the group of Rene van Lier. After receiving my PhD, I moved to Rijeka to work as a postdoc in the group of Bojan Polić. In 2012, I widended the scope of my research to investigate the role of immune cells in the development of metabolic diseases such as Diabetes Mellitus type 2. In 2015, I started my own group. The focus of my team is twofold. Several members investigate fundamental CD8 T cell biology, with a focus on memory formation. The other half in investigates how activated immune cells contribute to the early inflammatory processes that take place in obesity-induced, metabolically stressed tissues such as adipose tissue and the liver.

Assoc. Prof. Felix M. Wensveen

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Publications

• Šestan M, Mikašinović S, Benić A, Wueest S, Dimitropoulos C, Mladenić K, Krapić M, Hiršl L, Glantzspiegel Y, Rasteiro A, Aliseychik M, Cekinović Grbeša Đ, Turk Wensveen T, Babić M, Gat-Viks I, Veiga-Fernandes H, Konrad D, Wensveen FM, Polić B. An IFNγ-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate antiviral immune response. Nat Immunol .2024 Jun;25(6):981-993. doi: 10.1038/s41590-024-01848-3.

• Mladenić K, Lenartić M, Marinović S, Polić B, Wensveen FM. The "Domino effect" in MASLD: The inflammatory cascade of steatohepatitis. Eur J Immunol. 2024 Feb 5:e2149641. doi: 10.1002/eji.202149641.

• Gašparini D, Wensveen FM, Turk Wensveen T. Inflammageing mediated by cytotoxic lymphocytes is associated with diabetes duration Diabetes Res Clin Pract. 2023 Diabetes Res Clin Pract. 2024 Jan;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.

• 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/metabo1302015

• Gašparini D, Kavazović I, Barković I, Maričić V, Ivaniš V, Samsa DT, Peršić V, Polić B, Turk Wensveen T, Wensveen FM., Extreme anaerobic exercise 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.

• 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 Jan 14:db210209. 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):22

• 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. DOI: 10.1016/j.diabres.2020.108637

• 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.

• Wensveen FM, Šestan M, Turk Wensveen T, Polić B., 'Beauty and the beast' in infection: How immune-endocrine interactions regulate systemic metabolism in the context of infection. Eur J Immunol. 2019 Jul;49(7):982-995. doi: 10.1002/eji.201847895.

• Grčević D, Šućur A, Wensveen F., Croatian Immunological Society: Our half century. Eur J Immunol. 2019 Feb;49(2):208-211. doi: 10.1002/eji.201970025.

• Kavazović I, Polić B, Wensveen FM, Cheating the hunger games; Mechanisms controlling clonal diversity of CD8 effector and memory populations. Front Immunol. 2018 Nov 29;9:2831. doi: 10.3389/fimmu.2018.02831

• Jelenčić V, Šestan M, Kavazović I, Lenartić M, Marinović S, Holmes TD, Prchal-Murphy M, Lisnić B, Sexl V, Bryceson YT, Wensveen FM, Polić B. NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development. Nat Immunol. 2018 Oct;19(10):1083-1092. doi: 10.1038/s41590-018-0209-9.

• 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, Polić B. NKG2D: A Master Regulator of Immune Cell Responsiveness. Front Immunol. 2018 Mar 8;9:441. doi: 10.3389/fimmu.2018.00441.

• Jelenčić V, Lenartić M, Wensveen FM, Polić B, NKG2D: A versatile player in the immune system. Immunol Lett. 2017 Sep;189:48-53. doi: 10.1016/j.imlet.2017.04.006.

• Kavazović I, Lenartić M, Jelenčić V, Jurković S, Lemmermann NAW, Jonjić S, Polić B, Wensveen FM, NKG2D stimulation of CD8+ T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice. Eur J Immunol. 2017 Jul;47(7):1123-1135. doi: 10.1002/eji.201646805.

• Lenartić M, Jelenčić V, Zafirova B, Ožanič M, Marečić V, Jurković S, Sexl V, Šantić M, Wensveen FM, Polić B. NKG2D Promotes B1a Cell Development and Protection against Bacterial Infection. J Immunol. 2017 Jan 13. pii: 1600461. doi: 10.4049/jimmunol.1600461.

• Mikolasevic I, Milic S, Turk Wensveen T, Grgic I, Jakopcic I, Stimac D, Wensveen F, Orlic L. Nonalcoholic fatty liver disease - A multisystem disease? World J Gastroenterol. 2016 Nov 21;22(43):9488-9505. Review. DOI: 10.3748/wjg.v22.i43.9488

• Wensveen FM, Slinger E, van Attekum MH, Brink R, Eldering E. Antigen-affinity controls pre-germinal center B cell selection by promoting Mcl-1 induction through BAFF receptor signaling. Sci Rep. 2016 Oct 20;6:35673. doi: 10.1038/srep35673.

• Slinger E, Wensveen FM, Guikema JE, Kater AP, Eldering E. Chronic lymphocytic leukemia development is accelerated in mice with deficiency of the pro-apoptotic regulator NOXA. Haematologica. 2016 Sep;101(9):e374-7. doi: 10.3324/haematol.2016.142323. PubMed PMID: 27479816; DOI: 10.3324/haematol.2016.142323

• Sagiv A, Burton DG, Moshayev Z, Vadai E, Wensveen F, Ben-Dor S, Golani O, Polic B, Krizhanovsky V. NKG2D ligands mediate immunosurveillance of senescent cells. Aging (Albany NY). 2016 Feb;8(2):328-44. DOI: 10.18632/aging.100897

• Wensveen FM, Valentić S, Šestan M, Turk Wensveen T, Polić B. The "Big Bang" in obese fat: Events initiating obesity-induced adipose tissue inflammation. Eur J Immunol. 2015 Sep;45(9):2446-56. doi: 10.1002/eji.201545502.

• Wensveen FM, Valentić S, Šestan M, Wensveen TT, Polić B. Interactions between adipose tissue and the immune system in health and malnutrition. Semin Immunol. 2015 Sep;27(5):322-33. doi: 10.1016/j.smim.2015.10.006. Review.

• 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, Geest CR, Libregts SF, Derks IA, Ekert PG, Labi V, Villunger A,  Nolte MA, Eldering E. BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis. Apoptosis. 2013 Nov;18(11):1306-18. doi: 10.1007/s10495-013-0890-y.

• Trsan T, Busche A, Abram M, Wensveen FM, Lemmermann NA, Arapovic M, Babic M, Tomic A, Golemac M, Brinkmann MM, Jäger W, Oxenius A, Polic B, Krmpotic A, Messerle M, Jonjic S. Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16550-5. doi: 0.1073/pnas.1310215110.

• Wensveen FM, Lenartic M, Jelencic V, Lemmermann NA, ten Brinke A, Jonjic S, Polic B. NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase. J Immunol. 2013 Augv1;191(3):1307-15. doi: 10.4049/jimmunol.1300670.

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