Adaptive Immunity In Pathogenesis Of Atopic March
Reference : PhD Student
Publication de l'offre : 23 mars 2017
Atopic diseases, including atopic dermatitis (AD), asthma and food allergy, are closely related inflammatory diseases. They share common features of “atopy” (commonly known as allergy), showing exaggerated immune response to allergens, such as the production of specific IgE to allergens, and type 2 T helper (Th2) allergic inflammation. It is well known in clinic that an individual
often experiences the progression from AD to asthma. This mysterious phenomenon is called the “atopic march”. We have previously uncovered that cytokine TSLP produced by AD skin is a key mediator for the atopic march, but the underlying cellular and molecular mechanisms remain to be elucidated.
Recently, a new CD4+ helper cell subset, T follicular helper (Tfh) cell, has emerged to be a critical player in adaptive immunity by providing critical help to B cells. Based on our preliminary studies, we hypothesize that Tfh cell is an unrecognised player in the puzzle of the “atopic march”.
This thesis project aims at investigating the in vivo differentiation and maintenance of Tfh, the regulation of Tfh cell response by TSLP, and delineating the pathogenic role of Tfh and Th2 in the atopic march. To this aim, we will employ a newly developed
mouse model for the atopic march by using an innovative technology to deliver allergen through skin route and to induce airway allergic asthma. We will first aim to identify and characterize the Tfh cells in the lymphoid organs following
skin sensitization using cellular and immunological approaches (e.g. surface and intracellular staining, flow cytometry). We will then elucidate how TSLP in driving Tfh-GC response using the TSLP-overexpression and TSLP-conditional knockout mice. We will further study the pathogenic role of Tfh-GC response
and Th2 cell response in the atopic march leading to allergic asthma.
In this project, we will combine in vivo mouse studies (including conditional gene knockout, specific cell-depleting tools), immunological approaches (flow cytometry, adoptive transfer of immune cells), the in vitro cell culture and coculture system; molecular biological approaches, including qRT-PCR and RNAseq for gene expression and imaging.
The project is expected to provide novel insights into the redefinition of the mechanisms involved in the initiation and maintenance of adaptive immune response in the “atopic march”, which will hopefully lead to potential therapeutic applications for the treatment/prevention of atopic diseases.
We wish to integrate in the team a highly motivated, hard-working and collaborative PhD student. He/she should have solid knowledge in cellular and immunological biology, molecular biology, advanced microscopy and imaging, and have great enthusiasm on developing novel technologies and on exploring
pathogenesis of inflammatory diseases. He/she should have a good level of English speaking, reading and writing.
The student will acquire interdisciplinary research experience on inflammation and immunity, cell signaling, imaging, and functional mouse genetics. He/she will develop technique expertise flow cytometry, quantitative gene expression, deep sequencing, imaging as well as in vitro cell culture and in vivo pathophysiology. He/she should also acquire scientific expertise on designing, organizing and analyzing research experiments, oral presentation and paper writing.
Date limite de candidature : 1 novembre 2017