4 départements de recherche
750 employés
45 nationalités
55 équipes de recherche
16 lauréats ERC
260 publications par an
24000 m² de laboratoires

Soutenez-nous via

Fondation universite de Strasbourg

photo

Chef d'équipe

Mei LI
mei.li@igbmc.fr
Tel. : +33 (0)3 88 65 34 68

Les chiffres

52 équipes de recherche
134 chercheurs
95 post-doctorants
132 doctorants
194 ingénieurs & techniciens
22 masters
132 administratifs & services généraux 110 personnels ICS

Accès direct

Recrutement

Adaptive Immunity In Pathogenesis Of Atopic Dermatitis

Reference : PhD Mei LI

Publication de l'offre : 6 avril 2016

The goal of the thesis project is to achieve a better understanding of the adaptive immunity in pathogenesis of atopic dermatitis (AD). Being one of the most common inflammatory skin diseases, AD is characterized by chronic cutaneous inflammation, hyper IgE and T helper type 2 (Th2) response, and is closely related to other atopic diseases such as asthma. These atopic diseases show dramatic rise in prevalence, and have become alarmingly common. It is thus crucial to acquire a better understanding of the pathogenesis of these inflammatory diseases and to develop effective prevention and treatment strategies.

Our previous research using functional mouse genetic tools has established a number of mouse models for AD [1-5]. We discovered a key role of thymic stromal lymphopoietin (TSLP), a cytokine produced by keratinocytes, in instructing the Th2 inflammatory response [1-5]. Using these mouse models, we recently studied the immune cascade underlying how TSLP promotes Th2 immune response by coordinating the interplay between different immune cells [2]. In addition, we uncovered a counter-regulation between TSLP-driven Th2 immune axis and IL-23-driven Th17 immune axis, which shapes the inflammation of barrier-defective skin [6]. Adaptive immunity plays a central role in AD pathogenesis.

Recently, a new CD4+ helper cell subset, T follicular helper (Tfh) cell, has emerged to be a critical player in humoral immunity by providing help to B cells. However, the pathogenic role of Tfh cells in the context of AD and other atopic diseases remains unexplored. We will employ our originally established AD mouse models (TSLP-overexpressing model and cutaneous allergen sensitization model) to investigate

1) the Tfh cell differentiation, function and regulation in AD pathogenesis;

2) network regulation between dendritic cells (DCs), Tfh cells and B cells in the initiation and maintenance of adaptive immunity of AD;

3) regulation between Tfh and effector Th2 cells.

To achieve these goals, the project will employ mouse genetic engineering (e.g. inducible mouse knockout in different immune cells; specific depletion of immune cells; reporter mice), cellular and immunological approaches (e.g. surface and intracellular staining, flow cytometry, adoptive transfer of immune cells,
culture and co-culture of cells), molecular biological approaches (e.g. qRT-PCR, RNAseq) and imaging (e.g. confocal microscopy). We expect that the results will provide novel insights into the mechanisms underlying the inflammatory response in AD pathogenesis.

References :
1. Li, M., et al., J Invest Dermatol, 2009. 129(2): p. 498-502.
2. Leyva-Castillo, J.M., et al., Nat Commun, 2013. 4: p. 2847.
3. Li, M., et al., Proc Natl Acad Sci U S A, 2006. 103(31): p. 11736-41.
4. Li, M., et al., Proc Natl Acad Sci U S A, 2005. 102(41): p. 14795-800.
5. Zhang, Z., et al., Proc Natl Acad Sci U S A, 2009. 106(5): p. 1536-41.
6. Li, J., et al., J . Allergy Clin. Immunol., 2016. in press.

- COMPETENCES SOUHAITEES : 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, with an excellent level of English speaking, reading and writing.

- EXPERTISES QUI SERONT ACQUISES AU COURS DE LA FORMATION : 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.

Votre candidature

Date limite de candidature : 31 décembre 2016

Imprimer Envoyer

Université de Strasbourg
INSERM
CNRS

IGBMC - CNRS UMR 7104 - Inserm U 964
1 rue Laurent Fries / BP 10142 / 67404 Illkirch CEDEX / France Tél +33 (0)3 88 65 32 00 / Fax +33 (0)3 88 65 32 01 / directeur.igbmc@igbmc.fr