NCN POLONEZ 3
Targeted exosome-mediated crosstalk between epithelial and antigen presenting cells for effective immunity at barrier sites
dr Danuta Gutowska-Owsiak
Body barriers (such as skin, gut, respiratory tract, oral and other mucosal tissues) are specific sites of the interaction between the organism and the external world. To face the challenge, barrier tissues have multiple immunological functions and are capable of influencing both the magnitude and direction of innate and adaptive immune responses. Since these sites are the points of pathogen entry, constantly exposed to microbial threats, multiple mechanisms must exist that enable fast response to the invading pathogens, in order to maintain the homeostasis and integrity of organism. Indeed, epithelial surfaces facing the environment are exceptionally well equipped and often contain unique characteristics suited to provide essential barrier functions, such as stratified epidermis or production of antimicrobial peptides. In addition, epithelial cells may also present antigens as non-professional presenting cells thus contributing to downstream immune response from specific T cells, as it was shown for peptide antiens.
Recently, novel findings were published on the specific recognition of lipids by skin-homing T cells, responding to antigens presented by the CD1a molecule, especially enriched in Langerhans cells residing within the epidermis. Presentation by lipid ligands involves activity of phospholipase A2 (PLA2), which was shown to generate novel lipids promoting specific responses in the skin. We aim to understand if PLA2 produced by the epithelial cells (keratinocytes in our mode system of the skin) could contribute to this process. Specifically, the role of exosomes and other extracellular vesicles is of our primary interest. The project will investigate the crosstalk between the epithelial component of the barrier and the cells of immune system.
Danuta Gutowska-Owsiak, MD, PhD - Principal Investigator
2010 - PhD in Infection and Immunity, University of Liverpool, UK
2003 - Medical doctor (MD) degree, Medical University of Gdańsk, Poland
Oct 2017 - present: Principal Investigator/Assistant professor; Experimental and Translational Immunology Group; Intercollegiate Faculty of Biotechnology; University of Gdańsk – Medical University of Gdańsk, Poland
Oct 2017 - present: Academic Visitor; University of Oxford; Radcliffe Department of Medicine
Sept 2009 - Sept 2017: Postdoctoral/Senior postdoctoral immunologist; Weatherall Institute of Molecular Medicine University of Oxford, UK; MRC Human Immunology Unit, Cutaneous Immunology Group (Prof Graham Ogg)
June 2006: Visiting Scholar; INSERM, Paris, France (Prof Nicole Casadevall)
Oct 2005 - Sept 2009: PhD student; University of Liverpool, UK, School of Clinical Sciences (Supervisors: Dr Laszlo Pazmany, Dr Stephen E Christmas, Prof Martin Birchall)
2004 - 2005: Research assistant (honorary) at Academic Rheumatology Unit, University of Liverpool, UK (Prof Robert Moots)
• Journal reviews
2017 - Gutowska-Owsiak, D. and G.S. Ogg, Therapeutic vaccines for allergies; npj Vaccines 2,12 (2017)
2013 - Gutowska-Owsiak, D. and G.S. Ogg, Cytokine regulation of epidermal barrier, Clin Exp Allergy. 2013 Jun;43(6):586-98
2011 - Gutowska-Owsiak D. and Ogg GS. The epidermis as an adjuvant. J Invest Dermatol, 2012. 132(3 Pt 2): p. 940-8.
• Research articles
2017 - Wang X, Gutowska-Owsiak D, Salimi M, Kumar TA, Gwela A, Chen L, Wang Y, Giannoulatou E, Graham GS. Deficiency of filaggrin leads to impaired skin barrier function via regulating keratinocytes endogenous cysteine proteases activity; Clin Exp Dermatol. 2017 Aug;42(6):622-631
2016 - Ka Lun Cheung, Rachael Jarrett, Sumithra Subramaniam, Maryam Salimi, Danuta Gutowska-Owsiak, Yi-Ling Chen, Clare Hardman, Luzheng Xue, Vincenzo Cerundolo, and Graham Ogg ; Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a; J Exp Med; 2016 Oct 17; vol. 213 no. 11
2015 - Jarrett R, Salio M, Lloyd-Lavery A, Subramaniam S, Bourgeois E, Archer Ch, Cheung K, Hardman C, Chandler D, Salimi M, Gutowska-Owsiak D, de la Serna JB, Fallon P, Jolin H, Mckenzie A, Dziembowski A, Podobas E, Bal W, Johnson D, Moody B, Cerundolo V, Ogg GS. Filaggrin inhibits generation of CD1a neolipid antigens by house dust mite derived phospholipase; Sci Transl Med. 2016 Feb 10;8(325):325ra18
2015 - Chandima Jeewandara, Laksiri Gomes, N. Munasainghe, Danuta Gutowska-Owsiak, Dominic Waithe, S.A. Paranavitana, N.L.A. Shyamali, Graham S. Ogg and Gathsaurie Neelika Malavige; Platelet activating factor contributes to vascular leak in acute dengue infection; PLoS Negl Trop Dis. 2015 Feb 3;9(2)
2014 - Marwah I, Wang X, Chan H, Ogg GS‡, Gutowska-Owsiak D‡*. Filaggrin-deficiency in keratinocytes influences responsiveness of allergen-specific T cells to cognate antigen and compounds barrier function deficiency; Clin Immunol; 2014 Apr 29;153(1):153-155
2014 - Gutowska-Owsiak D*, Greenwald L, Watson C, Selvakumar TA, Wang X, Ogg GS. Histamine synthesizing enzyme, histidine decarboxylase, is upregulated by keratinocytes in atopic skin; Br J Dermatol. 2014 Oct;171(4):771-8
2013 - Gutowska-Owsiak D*, Salimi M, Selvakumar TA, Wang X, Taylor S, Ogg GS. Histamine exerts multiple effects on expression of genes associated with epidermal barrier function; J Invest Allergy Clin Immunol, 2014, Vol. 24(4): 231-239
2013 - Gutowska-Owsiak D*, Salimi M, Selvakumar TA, Taylor S, Ogg GS. Histamine enhances keratinocyte-mediated resolution of inflammation by promoting wound healing and response to infection; Clin Exp Dermatol. 2014 Mar;39(2):187-952.
2013 - Salimi M, Barlow J, Saunders S, Xue L, Gutowska-Owsiak D, Wang X, Huang L, Johnson D, Scanlon S, Fallon P, McKenzie AN, Ogg GS, A role for IL-25 and IL-33–driven type-2 innate lymphoid cells in atopic dermatitis; J Exp Med. 2013 Dec 16;210(13):2939-503.
2013 - Jankowska A, Gutowska-Owsiak D, Kamińska B, Liberek A. Osteoprotegerin and soluble receptor activator of nuclear factor kappa-B ligand in children with inflammatory bowel disease, Prz Gastroenterol 2013; 8 (3): 191–196
2013 - Gutowska-Owsiak D*, Birchall MA, Moots RJ, Christmas SE and Pazmany L. Expanded Population of CD1d-restricted Vα24+ Cells in a patient with active Rheumatoid Arthritis; Clin Immunol, 2014, 150 (2): 140–142
2013 - Gutowska-Owsiak D*, Moots RJ, Birchall MA, Christmas SE, Pazmany L. Proliferatory defect of invariant population and accumulation of non-invariant CD1d-restricted Natural Killer T cells in the joints of RA patients; Modern Rheumatology, Epub: 4Nov 2013
2011 - Gutowska-Owsiak D*, Schaupp AL, Salimi M, Selvakumar TA, McPherson T, Taylor S, Ogg GS. IL-17 downregulates filaggrin and affects epidermal barrier function gene expression; Exp Dermatol, 2012. 21(2): p. 104-10
2011 - Gutowska-Owsiak D*, Schaupp AL, Salimi M, Taylor S, Ogg GS. IL-22 down-regulates filaggrin expression and affects expression of profilaggrin processing enzymes, Br J Dermatol, 2011; 165 (3): 492-498
2008 - Birchall MA, Bailey M, Gutowska-Owsiak D, Johnston N, Inman CF, Stokes CR, Postma G, Pazmany L, Koufman JA, Phillips A, Rees LE. Immunologic response of the laryngeal mucosa to extraesophageal reflux. Ann Otol Rhinol Laryngol. 2008 Dec;117(12):891-5.
2008 - Rees LE, Pazmany L, Gutowska-Owsiak D, Inman CF, Phillips A, Stokes CR, Johnston N, Koufman JA, Postma G, Bailey M, Birchall MA. The mucosal immune response to laryngopharyngeal reflux. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1187-93.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions.
Grant agreement No. 665778.
Project is conducted within POLONEZ funding programme of National Science Centre POLAND.
Fellowship registration number: UMO-2016/23/P/NZ6/04056