Unit of System Toxicology

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The aim of our research is to understand the interaction between environmental exposures, the immune system and human health. 

Due to immunological memory, past environmental exposures shape present immune function. These exposures do not only include factors that impact adaptive immune memory, but also agents that shape innate immune responses for prolonged periods of time, moulding susceptibility to chronic inflammatory diseases including allergies and autoimmunity.  An especially sensitive period for environmental factors modulating immunity is early in life, and the human microbiome may have important functions in health and disease.

In our project, we focus on how different environmental exposures, including environmental and endogenous microbes, nanomaterials and chemicals, affect human wellbeing. We are especially interested in epithelial barriers and how exposure to external agents or colonization by opportunist microbes impacts on barrier function and immunity and systemic immune responses. Our aim is to uncover the mechanisms behind the factors linking environmental exposures with immune tolerance and the breaking of immune tolerance.

We work with data deriving from large human cohorts and clinical studies, and validate the results using in vivo and in vitro models. We carry out genomic, transcriptomic and proteomic analyses, and interpret the results using various bioinformatics methods. Our unit collaborates with many research groups around the world, and we participate in several international research consortia funded by the European Commission.

Head of Unit

Professor

Harri Alenius

Organizational unit: System toxicology
E-mail: harri.alenius@ki.se

Unit members

Harri AleniusProfessor
Nanna FyhrquistSenior researcher
Maura KereResearch administrator
Noora OttmanPostdoc

Projects

Karelian Allergy Project - KARA

This study focuses on the regions of Finnish and Russian Karelia, which are geographically very similar, but have a dramatic difference in the prevalence of allergies and asthma. The biodiversity hypothesis suggests that reduced exposure to diverse environmental microbes has resulted in the current increase in chronic inflammatory diseases in western societies. We have shown that the living environment, the skin microbiota, and the prevalence of allergies are interrelated, with children living in more rural areas having a richer microbiota on their skin, and suffering less frequently from allergic diseases compared with children living in the cities. Currently we are investigating in depth the association between genome-wide epigenetic markers and gene expression profiles in blood leukocytes, the composition of the skin microbiota, and the living environment of these children.

Microbes in Allergy and Autoimmunity Related to the Skin - MAARS

This project is an EU-funded, international study exploring the nature and duration of microbial stimuli and associated changes in the epithelial barrier leading to the development of skin-related allergy and autoimmunity. Atopic dermatitis and psoriasis serve as models for investigation of the programming of the immune system towards an allergic or autoimmune inflammation. The aim of the study is to identify microbe-host-interaction networks involved in the initiation, development and persistence of atopic dermatitis and psoriasis. The project will pave the way for progress in prevention, new diagnostic strategies and treatment options for allergy and autoimmunity related skin diseases.

Allergic and irritant contact dermatitis

Contact dermatitis (CD) is a highly frequent disease with significant impact on the quality of life, presenting major challenges in working life. Two major types of CD are recognized, including irritant and allergic CD. Diagnosis is based on allergy testing, exposure specification and careful follow-up, but the interpretation of patch test results is not always straightforward. Dermatologists currently lack reliable diagnostic tools and the purpose of the project is to develop a method for improved diagnostics.

Nanosolutions

Safety is a prerequisite for the public success of nanotechnology and therefore it is critical to develop methods that give better prediction of the biological effects and risks of engineered nanomaterials (ENM) for human health and the environment. Simple, fast and cost efficient, and yet reliable methods are required to meet the challenge of the ever-decreasing time between the development of new ENM and their marketing. The overarching aim of the EU-funded NANOSOLUTIONS project is to provide a means to develop a safety classification of ENM based on an understanding of their interactions with living organisms at the molecular, cellular, and organism levels. The objective is to determine the “biological identity” of ENM, and based on that, to develop a computational predictive tool for the assessment of ENM safety, i.e. ENM SAFETY CLASSIFIER. Various OMICS methods (e.g. microarrays, RNA-sequencing, proteomics) have been used to assess global expression levels of mRNA, miRNA and proteins from cells and organisms in response to ENM. In addition to proof-of-concept of ENM SAFETY CLASSIFIER, the project provides by far largest multi-layer OMICs data library derived from the robust cells and study organisms in response to large set of 31 carefully characterized ENM. Computation predictive tool for assessment of ENM safety is an important step towards fast, reliable and affordable ENM safety classification.