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Project #17060
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#17060 : Understanding IL-23 role in chronic inflammatory diseases in innate and adaptative immune cells
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Organisms :
Group :
Name of Applicant : Tharshana STEPHEN
Date of application : 22-06-2021
Unit : Immunoregulation
Location : Metchnikoff - 5th floor - room 20-21
Phone : 06 82 04 93 45
@ Mail : tharshana.stephen@pasteur.fr
@ PI-Mail : lars.rogge@pasteur.fr

Project context and summary :

The chronic inflammatory diseases (CID), as psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis (SpA), are clinically heterogeneous conditions that share common inflammatory pathways and derive from aberrant immune responses. GWAS strongly suggests that the IL-23/IL-17 pathway plays a key role in several CID. The successful treatment of psoriasis, PsA and axial SpA with IL-17A inhibitors has been validated. Interestingly, in literature, a strong GWAS association of IL23R with SpA was shown and IL-17A was shown to be downstream of IL-23 in murine CD4+ T cells. Surprisingly, a recent phase 2 study testing the IL-23 inhibitor risankizumab did not show any clinically improvement compared to placebo in patients with active axial SpA, whereas it has proven effective for the treatment of psoriasis and PsA. The reasons underlying the failure of IL-23 blocking in axial SpA are not known. Our understanding of the pathogenic mechanisms of these diseases is therefore limited, and the role of IL-23 needs to be studied. The specific question we want to address with this project is what are the gene induced by IL-23 in immune cell populations.


Related team publications :
Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo. Menegatti S, Guillemot V, Latis E, Yahia-Cherbal H, Mittermüller D, Rouilly V, Mascia E, Rosine N, Koturan S, Millot GA, Leloup C, Duffy D, Gleizes A, Hacein-Bey-Abina S; Milieu Intérieur Consortium, Sellam J, Berenbaum F, Miceli-Richard C, Dougados M, Bianchi E, Rogge L. Ann Rheum Dis. 2020 Dec 2:annrheumdis-2020-218304. doi: 10.1136/annrheumdis-2020-218304.
The IL-23/IL-17 pathway in human chronic inflammatory diseases-new insight from genetics and targeted therapies. Bianchi E, Rogge L. Genes Immun. 2019 May;20(5):415-425. doi: 10.1038/s41435-019-0067-y.
Service Delivery
Project Manager : vincent.guillemot@pasteur.fr
Project Type : Medium
Status : In Progress


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