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About

Type I interferons (IFN-I) are multifunctional cytokines that act locally and systemically in many physiological and pathological processes, sometimes in a paradoxical way. Although widely used in clinical application, IFN-I can become pathogenic in chronic infections and in autoimmune and inflammatory diseases. Our Unit investigates cell-intrinsic molecular mechanisms mediating and regulating IFN-I responses in human cells. We also focus on the direct effect of IFN-I on T cell-mediated immune response and on the impact of TYK2 variants in autoimmunity. We deem that knowledge of signaling mechanisms ensuring a balanced IFN-I response and return to homeostasis is essential to understand immunological processes and to translation into clinical application. Our recent study of ISG15-deficient patients illustrates how disruptive the lack of a subtle signaling retrocontrol can be to the equilibrium of the immune system. As a whole, our research aims at bridging molecular analysis to human physiology and pathogenesis. Conceptually, our findings can serve as paradigm for other cytokine systems and may direct the development of innovative therapeutics to better utilize IFN or to target its activity.

Former Members

2000
2000
Name
Position
2015
2019
Umeshree Govender
PhD Student
2015
2019
Béatrice Corre
Technician
2015
2019
Aïda Meghraoui
Post-doc
2015
2019
Nassima Messal
Post-doc

Projects

Project
Ongoing
3 Members

TYK2 variants in cytokine signaling and autoimmune diseases

Sandra Pellegrini (PI)

TYK2 belongs to the Janus/JAK family of protein tyrosine kinases and is involved in signaling of immunoregulatory cytokines (type I and type III IFNs, IL-6, IL-10 and IL-12 families) that contribute to a balanced […]
Project
Ongoing
2 Members

IFN-I and translational control

Sandra Pellegrini (PI)

We have investigated whether IFN-I activates the mTOR translational control pathway and to what extent the control of mRNA translation contributes to IFN α2/β responses. General questions have been addressed by a genome-wide search […]
Project
Ongoing
2 Members

Exploring a link between ISGylation and cell cycle via SKP2

Sandra Pellegrini (PI)

We recently uncovered a potentially interesting connection between ISGylation and cell cycle regulation. We reported that the degradation of USP18, major negative regulator of IFN-I signaling, involves SKP2, a well known actor in cell […]
Project
Ongoing
2 Members

ISG15 contribution to tuning of IFN-I activity and interferonopathies

Sandra Pellegrini (PI)

We have reported on the implication of the ubiquitin-like ISG15 protein in the negative regulation of IFN-I response in humans. ISGylation is a major post-translational modification whereby numerous proteins are conjugated to ISG15, with […]
Project
Ongoing
2 Members

Fine-tuning of IFN-I response by USP18

Sandra Pellegrini (PI)

The type I IFN system needs to be regulated not only at the level of its production, but also at the level of responses. We have shown that cells that have responded to IFN-I […]
Project
Ongoing
6 Members

Cellular and molecular immunoprofiling of multiple sclerosis patients

Frédérique Michel (PI)

This project aims at providing new knowledge on the immunomodulatory effect of IFN-I in multiple sclerosis patients by using state-of-the-art technologies. An important challenge is the identification of cellular and molecular biomarkers of IFN […]
Project
Ongoing
6 Members

Role of IFN-I in the development of IL-10-producing CD4 T cells

Frédérique Michel (PI)

We have shown that IFN-I promotes development of human type 1 regulatory-like cells (Tr1) that produce the anti-inflammatory cytokine IL-10, and have studied the integration of T cell receptor (TCR) signal strength and CD28 […]

Fundings

Publications

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Contact

Phone: + 33 1 40613305 Email: sandra.pellegrini@pasteur.fr Address 25-28 Rue du Docteur Roux 75015, Paris France