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The influence of Aryl hydrocarbon receptor ligands on protective and pathological immune responses

Objective

The Aryl hydrocarbon receptor is an evolutionary conserved widely expressed transcription factor that mediates the toxicity of a substantial variety of exogenous toxins, but is also stimulated by endogenous physiological ligands. While it is known that this receptor mediates the toxicity of dioxin, this is unlikely to be its physiological function. We have recently identified selective expression of AhR in the Th17 subset of effector CD4 T cells. Ligation of AhR by a candidate endogenous ligand (FICZ) which is a UV metabolite of tryptophan causes expansion of Th17 cells and the induction of IL-22 production. As a consequence, AhR ligation will exacerbate autoimmune diseases such as experimental autoimmune encephalomyelitis. Little is known so far about the impact of AhR ligands on IL-17/IL-22 mediated immune defense functions. IL-22 is considered a pro-inflammatory Th17 cytokine, which is involved in the etiology of psoriasis, but it has also been shown to be a survival factor for epithelial cells. AhR is polymorphic and defined as high or low affinity receptor for dioxin leading to the classification of high and low responder mouse strains based on defined mutations. In humans similar polymorphisms exist and although on the whole human AhR is thought to be of low affinity in humans, there are identified mutations that confer high responder status. No correlations have been made with Th17 mediated immune responses in mice and humans. This study aims to investigate the role of AhR ligands and polymorphisms in autoimmunity as well as protective immune responses using both mouse models and human samples from normal controls as well as psoriasis patients.

Call for proposal

ERC-2008-AdG
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Host institution

MEDICAL RESEARCH COUNCIL
Address
North Star Avenue Polaris House
SN2 1FL Swindon
United Kingdom
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
EU contribution
€ 722 398,79
Principal investigator
Brigitta Stockinger (Dr.)
Administrative Contact
David Jones (Mr.)

Beneficiaries (3)

MEDICAL RESEARCH COUNCIL
United Kingdom
EU contribution
€ 722 398,79
Address
North Star Avenue Polaris House
SN2 1FL Swindon
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Principal investigator
Brigitta Stockinger (Dr.)
Administrative Contact
David Jones (Mr.)
CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL
Germany
EU contribution
€ 479 636,41
Address
Olshausenstrasse 40
24118 Kiel
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Susanne Neufeldt (Ms.)
TURUN YLIOPISTO
Finland
EU contribution
€ 40 316,40
Address
Yliopistonmaki
20014 Turku
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Eliisa Särkilahti (Dr.)