Current position: Group leader, "Immune tolerance and T cell differentiation", Center of Immunology Marseille-Luminy (CIML), France
Contact: Magali.Irla@inserm.fr
2019: Laureate of the French National Academy of Medicine
2016: Habilitation à Diriger des Recherches (HDR)
Since 2013: Prinicpal Investigator (Marie Curie Reintegration grant); Center of Immunology Marseille-Luminy (CIML), France
Project: "Immunological tolerance: implication of thymic epithelial cells and regulatory T cells"
2010-2012: Junior group leader, Ambizione Fellow (Swiss National Science Foundation) - Department of Pathology and Immunology - University of Geneva Medical School, Switzerland. http://pathology.unige.ch/group-irla.html
Project: “Patterning and homeostasis of the thymic medulla, a microenvironment specialized in T cell tolerance induction”
2006-2010: Postdoctoral fellow (EMBO Long Term fellow), Pr. Walter Reith’s laboratory - Department of Pathology and Immunology - University of Geneva Medical School, Switzerland
Project: “Cellular and molecular mechanisms controlling the cellularity of Aire+ medullary thymic epithelial cells - key mediators of central T cell tolerance”
2001-2005: Ph.D. in Immunology, Dr. Catherine Nguyen’s laboratory - INSERM-U928 - University of Aix-Marseille II, France
Project: “Genomic and functional characterization of a gene expressed by thymic epithelial cells: Spatial”
2001: Master in Immunology, University of Aix-Marseille II
Magali Irla has a long-standind interest in understanding the mechanisms controlling the induction of T-cell tolerance in the thymus. The thymic medulla provides a specialized microenvironment dedicated for T-cell education. In particular, medullary thymic epithelial cells (mTECs) play a central role in this process by their unique capacity to activate a promiscuous gene-expression program leading to the synthesis of a large repertoire of peripheral self-antigens. This gene expression program is controlled by the Autoimmune Regulator (Aire), a transcription factor that is defective in the human disease autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED).
Her work has established that the cellularity of mTECs expressing Aire is controlled by antigen specific interactions with CD4+ thymocytes (Immunity 2008, Trends Immunol 2010). She further established that these interactions regulate the expansion and patterning of the thymic medulla (Front Immunol. 2015, J Immunol. 2013, PLoS One. 2012). In the context of these interactions, she showed that the cytokine lymphotoxin α fine-tunes the thymic entry of peripheral dendritic cells and macrophages, which regulates central tolerance (Nat. Commun 2018). She recently found that TGF-β signaling in thymocytes is crucial for efficient negative selection (Nat. Commun 2019). She also demonstrated the regenerative potential of the cytokine RANKL to restore thymic functions upon bone marrow transplantation (EMBO Mol Med 2017).
Finally, she extended her interest in the field of T-cell tolerance by studying the mechanisms controlling the maintenance of peripheral T-cell tolerance, with a particular emphasis on the role of plamacytoid dendritic cells (pDCs). She found that pDCs, via their ability to present Ags to CD4+ T cells, confer a natural protection against autoimmune disease development and thus can determine the outcome of adaptive immune responses in vivo (J Exp Med. 2010).
Current research interests:
This project is supported by a Marie Curie reintegration Grant from the European Commission - SIGNEPI4TOL project.
In this context, we recently identified that RANKL is naturally upregulated in the thymus during the early phase of thymic regeneration. The in vivo neutralization of RANKL impairs TEC recovery whereas ex vivo RANKL administration during bone marrow transplantation boosts thymic regeneration and T-cell production (EMBO Mol Med. 2017).
This project is supported by the ANR (Coordinator of the PRC, RANKLthym).
This project is supported by The Foundation ARC, a Proof of Concept funding from Inserm-Transfert and Fondation A*Midex prematuration.
Other activities:
- Since 2017-present: Review Editor, Frontiers in Immunology, “Section Alloimmunity and Transplantation”
- Since 2015-present: Review Editor, Frontiers in Immunology, “Section Immunological Tolerance and Regulation”
- Since 2013-present: Associate Editorial Board member, American Journal of Clinical and Experimental Immunology
Commentaries and previews on published work:
Passos GA, Mendes-da-Cruz DA, Oliveira EH. Editorial: The Role of Aire, microRNAs and Cell–Cell Interactions on Thymic Architecture and Induction of Tolerance. Front Immunol. 2015 Dec 14;6:615.
Bordon Y. Immune tolerance: Present and clear danger. Nat Rev Immunol. 2010 Sep;10(9):616.
Other links:
http://www.ciml.univ-mrs.fr/science/lab-magali-irla/immune-tolerance-and-t-cell-differentiation
https://loop.frontiersin.org/people/83580/impact
https://www.researchgate.net/profile/Magali_Irla
https://orcid.org/0000-0001-8803-9708