Cytotoxic T lymphocyte(blue) attacks target cell (green) and release lysosomal proteins (red)

T Cell Biology and Skin Inflammation

T lymphocytes (T cells) play a central role in the adaptive immune system and are vital for the maintenance of a healthy life. T cell progenitors originate in the bone marrow and subsequently develop in the thymus. Mature, naive T cells leave the thymus after very strict selection processes and start their recirculation between the blood and lymph. Upon encountering of specific antigens, the naïve T cells are activated via highly regulated processes. T cell activation results in the differentiate of T cells into effector and memory T cells. Recently, it has become clear that twice as many T cells are found in the skin as in the circulation. The majority of skin-resident T cells are memory T cells. Skin-resident T cells are important in our defence against pathogens and most probably play central roles in inflammatory skin diseases as allergic contact dermatitis, atopic dermatitis and psoriasis.

Our vision is to provide optimal prevention and treatment of inflammatory skin diseases. Our goal is to uncover novel pathways and molecules involved in T cell activation and differentiation and thereby new targets to modify T cell responses. Our mission is to unravel how disturbances in T cell activation and differentiation lead to inflammatory skin diseases.

Research focus areas

We explore mechanisms involved in T cell development, activation and differentiation focusing on the role of the microenvironment in thymus and skin, cytokines, vitamins, and environmental factors such as allergens and xenobiotics.

Our primary interest is T cell biology and inflammatory skin diseases. We focus on the role of filaggrin and other skin proteins in T cells development, vitamin D as a regulator of activation and differentiation of T cells, T cell responses during inflammatory skin diseases, crosstalk between T cells, antigen presenting cells and keratinocytes, and the role of skin-resident memory T cells versus systemic memory T cells during skin inflammation.

In our studies, we integrate in vitro, ex vivo and 3D skin models, various mouse models and patient samples to study T cell responses, how they are regulated and how they affect skin inflammation.

Senior group members:
Carsten Geisler, Professor, MD, PhD, DMSc., Group leader
Charlotte Menné Bonefeld, Associate professor, PhD
Martin Kongsbak-Wismann, Assistant professor, PhD

Junior group members include:
1 post docs
1 research assistant
6 PhD students
4 graduate students
1 technician/lab manager

About

Group Leader: Carsten Geisler

Head of Department of Immunology and Microbiology (ISIM) since 2002 with extensive experience in leadership and research management. At ISIM, 150 scientific and administrative staff members are employed.

ISIM has revenue of DKK 119 million (2017) of which the majority, 72%, is funding from private partners. Professor in molecular immunology since 2005 with special focus on T cell biology and the role of T cells in inflammatory skin diseases.

Author of more than 160 international peer reviewed journals and an H-index of 37 (Web of Science)/42 (Google Scholar). Supervisor for 23 PhD and 55 master students. Co-PI with Professor Jeanne Duus Johansen in the Clinical Academic Group (CAG) in Allergy since 2017.

In our group, we have extensive experience in cutting-edged analyses of the adaptive immune system in both humans and mice with special focus on the role of T cells, antigen presenting cells, keratinocytes and cytokines. We have established advanced in vitro studies of human and mouse T cells including isolation of specific T cell subsets, multi-colour flow cytometric analysis and single cell separation and sequencing.

We have established models in mice for inflammatory skin diseases, and we have developed a range of highly advanced methods to isolate and analyse single cells from the epidermis and dermis. We have elucidated T cell responses to single allergens and mixture of antigens in the skin of mice and humans, and recently described the existence and function of skin resident memory T cells.

Personal information
Born in 1956. Nationality: Danish. ORCID ID 0000-0002-8472-0771.

Education and Academic Degrees

  • 1982 Medical Doctor (MD), University of Copenhagen (UCPH), Denmark.
  • 1994 PhD in immunology, UCPH.
  • 1995 DMSc in medicine/immunology, UCPH.

Employment and Positions

  • 1982 – 1987 Resident and senior resident at medical, surgical and clinical immunological wards at University Hospitals in Copenhagen.
  • 1987 – 1990 Research scholar supported by the Danish Medical Research Council and by the Academy of Science.
  • 1990 – 1992 Senior research fellow supported by the Danish Cancer Society.
  • 1992 – 2005 Associate professor in molecular immunology, UCPH. 2005 – Full professor in molecular immunology, UCPH. 2007 – Head/Chairman of the Department of Immunology and Microbiology, UCPH.

Honorary Offices and Administration

  • 1999 – 2005 Member of the Scientific Committee of the Faculty of Health and Medical Sciences.
  • 2000 – 2006 Member/Chairman of the board of The Weimann Foundation.
  • 2002 – 2007 Head of the Department of Medical Microbiology and Immunology.
  • 2006 – 2011 Research leader for Copenhagen Cluster of Immunology.

Research interests
The immune system with focus on T cells, skin immunology and inflammation.

Referee
Referee at Cell, EMBO Journal, Journal of Immunology, Journal of Clinical Investigation, PloSONE, Critical Reviews in Immunology, Blood, Scandinavian Journal of Immunology, International Immunology, Molecular Immunology, Journal of Oral Pathology and Medicine and APMIS.

Grants and awards (2013 to present)

  • 2013 The Danish Council for Independent Research | Medical Sciences 2.592.000 Dkr.
  • 2013 Vera and Carl Johan Michaelsen Foundation 600.000 DKr.
  • 2014 The Faculty of Health and Medical Sciences 1.500.000 Dkr.
  • 2016 Læge Sofus Carl Emil Friis og hustru Olga Doris Friis Foundation 1.200.000 Dkr.
  • 2017 LEO Foundation 2.000.000 Dkr.
  • 2017 Copenhagen Health Science Partners 2.000.000 Dkr.
  • 2018 LEO Foundation 2.780.000 Dkr

Publications

  • Author and co-author of more than 165 international peer reviewed journals listed in PubMed.
  • Web of Science H-index 37, 4295 citations (January 2018)
  • Google Scholar H-index 42, 5632 citations (January 2018)

Charlotte Menné Bonefeld, associate professor, PhD


Research interests
The focus of my research is the immune response in healthy and diseased skin especially in inflammatory skin diseases as allergic contact dermatitis, psoriasis and atopic dermatitis. The focus of my research the last years has been to elucidate the role of IL-17A-producing cells (innate lymphoid cells,  T cells and tissue-resident CD8+ T cells) in skin inflammation and to study the effects of mixtures of contact allergens during the allergic response.

Publications

  • Author and co-author of 83 international peer reviewed journals listed in PubMed.
  • Web of Science H-index 21, 1319 citations (March 2018).

Martin Kongsbak-Wismann, Assistant professor, PhD

Research interests
The focus of my research is to unravel the molecular events underlying activation of the T cells of the immune system with special focus on the role of vitamin D during T cell activation. I have contributed by showing that vitamin D and the vitamin D receptor (VDR) is important not only for T cell activation but also for T cell differentiation. In order to make this research translational, I am currently involved in various projects investigating the role of vitamin D and T cell activation in relation to a variety of immunological diseases namely psoriasis and atopic dermatitis and in hereditary vitamin D resistant rickets (HVDRR).

Scientific degrees

  • B.Sc. in Molecular Biomedicine, 2009
  • M.Sc. in Molecular Biomedicine, 2011
  • Ph.D. in Immunology, 2014
  • Master of Business Administration (MBA), 2017

Publications
Author or co-author of 14 scientific articles and reviews in peer-reviewed journals listed in PubMed.
Web of Science H-index 7, 387 citations (March 2018)

Publications

Ten selected publications (2010-2017)

  1. von Essen, M. R., M. Kongsbak, P. Schjerling, K. Olgaard, N. Odum, and C. Geisler. 2010. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat. Immunol. 11: 344-349.
  2. Levring, T. B., A. K. Hansen, B. L. Nielsen, M. Kongsbak, M. R. von Essen, A. Woetmann, N. Odum, C. M. Bonefeld, and C. Geisler. 2012. Activated human CD4 T cells express transporters for both cysteine and cystine. Sci. Rep. 2: 266.
  3. Nielsen, M. M., P. Lovato, A. S. Macleod, D. A. Witherden, L. Skov, B. Dyring-Andersen, S. Dabelsteen, A. Woetmann, N. Odum, W. L. Havran, C. Geisler, and C. M. Bonefeld. 2014. IL-1beta-Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity. J. Immunol. 192: 2975-2983.
  4. Nielsen, M. M., B. Dyring-Andersen, J. D. Schmidt, D. Witherden, P. Lovato, A. Woetmann, N. Odum, S. S. Poulsen, W. L. Havran, C. Geisler, and C. M. Bonefeld. 2015. NKG2D-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Invest Dermatol. 135: 1311-1319.
  5. Bonefeld, C. M., T. H. Petersen, J. Bandier, C. Agerbeck, A. Linneberg, K. Ross-Hansen, S. Stender, P. B. Szecsi, J. D. Johansen, C. Geisler, and J. P. Thyssen. 2016. Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response. Br. J Dermatol. 175: 706-712.
  6. Willerslev-Olsen, A., T. Krejsgaard, L. M. Lindahl, I. V. Litvinov, S. Fredholm, D. L. Petersen, C. Nastasi, R. Gniadecki, N. P. Mongan, D. Sasseville, M. A. Wasik, C. M. Bonefeld, C. Geisler, A. Woetmann, L. Iversen, M. Kilian, S. B. Koralov, and N. Odum. 2016. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma. Blood 127: 1287-1296.
  7. Bonefeld, C. M., C. Geisler, E. Gimenez-Arnau, J. P. Lepoittevin, W. Uter, and J. D. Johansen. 2017. Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens. Contact Dermatitis 77: 133-142.
  8. Buus, T. B., N. Odum, C. Geisler, and J. P. H. Lauritsen. 2017. Three distinct developmental pathways for adaptive and two IFN-gamma-producing gammadelta T subsets in adult thymus. Nat. Commun. 8: 1911.
  9. Rode, A. K. O., M. Kongsbak, M. M. Hansen, D. V. Lopez, T. B. Levring, A. Woetmann, N. Odum, C. M. Bonefeld, and C. Geisler. 2017. Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNgamma Secretion. Front Immunol. 8: 656.
  10. Schmidt, J. D., M. G. Ahlstrom, J. D. Johansen, B. Dyring-Andersen, C. Agerbeck, M. M. Nielsen, S. S. Poulsen, A. Woetmann, N. Odum, A. R. Thomsen, C. Geisler, and C. M. Bonefeld. 2017. Rapid allergen-induced interleukin-17 and interferon-gamma secretion by skin-resident memory CD8+ T cells. Contact Dermatitis 76: 218-227.
Group members