BioMediTech Research Groups

Immunoregulation

Group Leader: Associate Professor Marko Pesu

marko.pesu(at)uta.fi

About Us

The Immunoregulation group investigates how the Proprotein convertase enzymes (PCSK) enzymes regulate the immune system.

A significant proportion of proteins are initially synthesised in an immature, non-functional form. The PCSK enzymes cleave and convert these pro-proteins into functional end products, and thereby serve as critical regulators of cellular homeostasis in both health and disease. Investigating PCSKs in the context of immunity will improve our understanding of the normal function of the immune system as well as the pathogenesis of immune-mediated diseases.

Achievements

We have previously shown that PCSKs are highly regulated in immune cells wherein they modulate both the adaptive and innate immune responses. Specifically, we have for example demonstrated that deleting a PCSK enzyme FURIN in T cells results in defective peripheral immune tolerance and erroneous T helper cell polarization. In macrophages FURIN inhibits the production of pro-inflammatory cytokines and generation of inflammatory macrophage phenotype. We have also explored the immunoregulatory role of PCSKs in non-mammalian model systems, fruit fly and zebrafish, and investigated the plasma PCSK levels in patient cohorts.

Collaboration offer and requests

Contact: marko.pesu(at)uta.fi

Major Publications

  1. Aittomäki S, Valanne S, Lehtinen T, Matikainen S, Nyman TA, Rämet M, Pesu M. Proprotein convertase Furin1 expression in the Drosophila fat body is essential for a normal antimicrobial peptide response and bacterial host defense. FASEB J. 2017 Nov;31(11):4770-4782.
  2. Vähätupa M, Aittomäki S, Martinez Cordova Z, May U, Prince S, Uusitalo-Järvinen H, Järvinen TA, Pesu M. T-cell-expressed proprotein convertase FURIN inhibits DMBA/TPA-induced skin cancer development. Oncoimmunology. 2016 Oct 14;5(12):e1245266.
  3. Cordova ZM, Grönholm A, Kytölä V, Taverniti V, Hämäläinen S, Aittomäki S,Niininen W, Junttila I, Ylipää A, Nykter M, Pesu M. Myeloid cell expressedproprotein convertase FURIN attenuates inflammation. Oncotarget. 2016 Aug23;7(34):54392-54404.
  4. Oksanen A, Aittomäki S, Jankovic D, Ortutay Z, Pulkkinen K, Hämäläinen S,Rokka A, Corthals GL, Watford WT, Junttila I, O’Shea JJ, Pesu M. Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii. J Immunol. 2014 Dec 1;193(11):5470-9.
  5. Turpeinen H, Oksanen A, Kivinen V, Kukkurainen S, Uusimäki A, Rämet M, Parikka M, Hytönen VP, Nykter M, Pesu M. Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a). J Biol Chem. 2013 Dec 20;288(51):36610-23.
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