PhD project on the modulation of the balance between inflammatory and physiological osteoclasts by inflammatory or protective T cells under anti-TNF therapy

A PhD position is proposed in team 2 on the modulation of the balance between inflammatory and physiological osteoclasts by inflammatory or protective T cells under anti-TNF therapy.

Modulation of the balance between inflammatory and physiological osteoclasts by inflammatory or protective T cells under anti-TNF therapy

Summary:

We have recently, demonstrated the existence of 2 osteoclast populations (physiological and inflammatory OCLs) that differ in their immune function (Ibanez et al, JBMR 2016) and that emergence of inflammatory osteoclasts relies on the combination of RANK-L, IL-17 and TNF-α produced by activated CD4+ T cells in disease condition (Ciucci et al, Gut 2015). Anti-TNF agents are the first line of treatment in IBD. Our preliminary data revealed that IBD mice treated with anti-TNF display a spectacular improvement of intestinal inflammation and bone destruction despite the persistence of activated T cells. This is discordant with their stimulatory role on osteoclasts. Therefore, the aims of this project are:
1. To investigate the effect of T cells that pesist in IBD mice treated +/- anti-TNF on the generation of physiological vs. inflammatory osteoclasts in vitro. To compare the T cell subsets generated +/- anti-TNF by RNAseq analysis to identify factors potentially involved in the control of each OCL subsets and characterize the related mechanisms involved in their effect. 3. To confirm the results in vivo by transferring the different T cell subsets in T cell deficient mice and evaluation of the bone phenotype and inflammatory status. 4/ validate the results in IBD patients.
The project will use a large set of methodolgical approaches : cell culture (immune and bone cells), animal models, flow cytometry, RNAseq, elisa, RT-qPCR, bioinformatics, histology, etc

 

Application:

We are seeking a highly motivated and talented PhD student with an excellent knowledge in immunology and cell biology. Excellent team, communication and organization skills are essential. French or English practice is mandatory.

To apply please send your CV, master records and motivation letter by mail at