Immunology of Epidermolysis Bullosa

From 2006 – 2009, Iris Gratz was a Postdoc at the  EB House Austria, a Centre of Expertise for Epidermolysis Bullosa (EB) and Special Clinic for “Butterfly Children”. Since then, the team is still working towards elucidating several aspects of the Immunology of Epidermolysis Bullosa. In collaboration with the team of the EB House Austria, Anshu Sharma, PhD (Postdoc) and Leonie Schöftner, MSc (research assistant) analyze the immunological consequences of skin gene therapy of EB patients. Additionally they also study the role of skin-tropic immune cells in the regulation of skin wound healing and cancer development. (Funding Debra Austria)

 

The “Allergy-Cancer-BioNano Research Centre” (ACBN)

Iris Gratz, PhD,moved from the University of California, San Francisco (UCSF) to Salzburg to join the PLUS and start the Immune Regulation Group in March 2014. The group was then invited to join “The Allergy-Cancer-BioNano Research Centre” (ACBN). Within ACBN we are supporting other groups with our expertise in animal science and collaborate on projects related to tumor immunology. Overall, the principal goal of our research is to investigate the mechanisms of immune regulation in peripheral tissues such as the skin. (Funding PLUS)

 

Immunity in Cancer and Allergy

The doctoral college is focused on two pathologies of the immune system, i.e. the overwhelming allergic immune response and the inefficient immune response against certain tumors. Both diseases are a growing concern and there is an urgent medical need to elucidate the underlying mechanisms for the development of new therapies. Unraveling the cellular and molecular immunological mechanisms and pathways enables to develop rational and molecule-based strategies for the treatment of these diseases. The aim of the doctoral college is to attract and select excellent graduate students from all over the world. (FWF Project DK-Plus W1213;  http://ica.sbg.ac.at)

 

Regulation of cutaneous tissue-repair by a specialized population of CD4+ T cells

Cutaneous Tissue-resident memory T cells (TRM) persist locally in the skin where they provide frontline defense against recurring insults. We have recently found that a fraction of these skin TRM cells can exit the tissue and be identified as a novel population of skin-tropic CLA+CD4+ T cells in the peripheral blood. These cells have a regulatory phenotype and likely participate in host-protective antimicrobial and wound healing responses following tissue damage. In this project, Suraj Varkhande, PhD (Postdoc) and Leonie Schöftner, BSc (Master’s student) work in close collaboration with the group of Daniel J. Campbell at the Benaroya Research Institute in Seattle, WA, USA. Together we use in vitro analyses, skin organoids and innovative humanized mouse models to assess the function of human TRM during cutaneous inflammation and wound healing. Funding by NIH.

 

Cutaneous Gamma Delta T cells play a central role in tumor defense

In addition to the aforementioned skin TRM cells, Cutaneous Gamma Delta T cells (specifically Vδ1+ T cells) have unique functions in the skin and play a central role in defense against cutaneous tumors. Together with  GammaDelta Therapeutics Giorgia Nasi, PhD (Postdoc) studies the biology of human cutaneous Vδ1+ T cells in skin-humanized mice. In this project we take advantage of the proprietary isolation and expansion protocols developed by GammaDelta Therapeutics to selectively generate Vδ1+ T cell populations suitable for clinical application. Additionally, Giorgia is interested in the role of cutaneous γδ T cells in the etiology of Epidermolysis Bullosa. Funded by GammaDelta Therapeutics.

 

HDACs as regulators of immunity

In barrier tissues, such as the skin, the decision between immune activation in response to pathogens versus tolerance is determined by the balance between suppressive regulatory T cells (Treg) and pro-inflammatory effector T cells (Teff). In addition to thymic Treg (tTreg) cells, peripherally generated Treg (pTreg) cells are crucial in regulating the response to innocuous antigens such as skin-specific self-antigens and commensals. Together with seven research groups from Vienna we test the hypothesis that histone deacetylases (HDACs) regulate the differentiation and function of T cells. Within the FWF-funded  SFB-F70 Gertrude Achatz, PhD, PD (Senior Scientist), Alice Taliento, MSc (PhD student) and Melanie Lietzenmayer, MSc (PhD student) focus on the role of HDACs in the generation of peripheral regulatory T cells. Specifically, we study the role of class I HDACs in pTreg generation, function and migration to the skin utilizing an experimental model for T cell-mediated skin autoimmune inflammation. FWF-funded  SFB-F70.

 

Iris Gratz is member of the following programs:

Funded by