Equipe-Loreadana-LAb-APreT2-e1548683559409

Team Saveanu / Guermonprez

Department Nephrology, Immunology and Hematology

 

Team leader

 

Line-up

 

Presentation

Antigen Presentation by Dendritic Cells to T cells

Dendritic cells (DCs) are the sentinel cells of the immune system. DCs present antigen to T lymphocytes and regulate their activation. T lymphocytes recognize and eliminate infected or cancer cells. Therefore, understanding the biology of T cell activation by DCs is crucial for the development of vaccines and immunotherapies. Also, inappropriate regulation of T lymphocyte activation by DCs supports the development of chronic inflammatory diseases and auto-immunity.

Our team investigates the mechanisms underpinning T cell activation by DCs. We implement multi-scale and multi-disciplinary approaches to tackle 3 research topics.

1- Ontogeny and dynamics of DC populations.

At homeostasis, DCs populations are continuously renewed from bone marrow hematopoietic stem cells. The dynamics of DCs population impacts on immune responses. We aim at understanding: i) the ontogenetic processes enabling the production of various DCs subsets (classical and inflammatory) and its regulation during cancer; ii) how DCs traffic to solid tumours. This project implements contemporary technologies such as high dimensional profiling, single cell RNAseq as well as humanised mice models. Building on a better understanding of DC populations, we design and evaluate therapeutic interventions aiming at increasing DC infiltration in solid tumours to stimulate anti-tumour immunity.

2- Antigen cross-presentation/presentation by MHCI/II.

In most instances, induction of antigen-specific T cell responses relies on the phagocytosis of particulate antigens by DCs. This is highly relevant for tumour antigens that are engulfed together with cancer cell debris. The dynamics of antigen-containing phagosomes is controlled by their interactions with multiple types of endosomes (early, storage, late, lysosomes). These interactions ultimately control the formation and presentation of antigenic peptides-MHC I and II complexes. We investigate if and how phagosome-associated proteins control phagosome dynamics and antigen presentation by MHCI/II to T lymphocytes in DCs subsets. Both, unbiased genetic screen using CRISPR-Cas9 and hypothesis driven approaches (Rab GTPases and PI3Kinases) are developed in the lab to tackle the molecular cell biology of antigen presentation by DCs.

3- T lymphocyte activation, fate and function.

The recognition of MHC-peptide complex by the T cell receptor leads to the formation of the immune synapse. We aim at understanding how intracellular trafficking in T lymphocytes supports the recognition of MHC-peptides complexes by the T cell receptor. Using intracellular live imaging, advanced microscopy techniques (FRET) and cutting-edge proteomics (in vivo biotynilation via APEX2), we investigate the endocytic mechanisms controlling TCR signalling at the DC-T cell synapse. Specifically, we are addressing how the balance between recycling or degradation of several key proteins for T cell activation such as TCRzeta, Lck and LAT controls signalling downstream TCR triggering.

In addition, we investigate the long-term consequences of antigen presentation by DCs subsets on the differentiation, fate and function of T lymphocytes. DCs are composed of multiple subsets which are also regulated by context-dependent signals. We are investigating how cell-intrinsic DCs features and environmental cues (including factors from the tumour micro-environment) shape the diversity of antigen-presenting DCs and anti-tumour T cell responses. In particular, we investigate how DCs imprint some trafficking behaviour in T cells and impact on T cell fate in the context of breast and lung cancer.

 

Landmark publications

  • Publication date : 02 June 2020 More

    New players in the activation of T Lymphocytes Nature Communications

    Autors : Evnouchidou Irini Pascal Chappert Benadda Samira Andres Zucchetti Mirjana Weimershaus Bens Marcelle Caillens Vivien Despoina Koumantou Lotersztajn Sophie Peter van Endert Jean Davoust Guermonprez Pierre Claire Hivroz David A. Gross Saveanu Loredana

  • Publication date : 01 October 2019 More

    Origin and development of classical dendritic cells. International Review of Cell and Molecular Biology. 2019, In press

    Autors : Guermonprez Pierre Yohan Gerber Kristine Vaivode Pierre Bourdely Julie Helft co-corresponding authors

  • Publication date : 02 September 2019 More

    Is there a place and role for endocytic TCR signaling? Immunol Rev. 2019 Sep;291(1):57-74.

    Autors : Saveanu Loredana Zucchetti AE Evnouchidou Irini Ardouin L Hivroz C

  • Publication date : 01 April 2019 More

    Inflammasome activation: a monocyte lineage privilege. Nat Immunol. 2019 Apr;20(4):383-385

    Autors : Guermonprez Pierre Helft J

  • Publication date : 20 March 2017 More

    IRAP+ endosomes restrict TLR9 activation and signaling Nat Immunol. 2017 May;18(5):509-518

    Autors : Babdor J Descamps D Adiko AC Tohmé M Maschalidi S Evnouchidou Irini Vasconcellos LR De Luca M Mauvais FX Garfa-Traore M Brinkmann MM Chignard M Manoury B Saveanu Loredana

  • Publication date : 20 December 2016 More

    The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells Immunity. 2016 Dec 20;45(6):1205-1218.

    Autors : Menezes S Melandri D Anselmi G Perchet T Loschko J Dubrot J Patel R Gautier EL Hugues S Longhi MP Henry JY Quezada SA Lauvau G Lennon-Duménil AM Gutiérrez-Martínez E Bessis A Gomez-Perdiguero E Jacome-Galarza CE Garner H Geissmann F Golub R Nussenzweig MC Guermonprez Pierre

  • Publication date : 17 July 2015 More

    Cross-Presentation of Cell-Associated Antigens by MHC Class I in Dendritic Cell Subsets Front Immunol. 2015 Jul

    Autors : Gutiérrez-Martínez E Planès R Anselmi G Reynolds M Menezes S Adiko AC Saveanu Loredana Guermonprez Pierre

 
 

Latest Publications

  • Publication date : 03 August 2020 More

    The protein kinase A negatively regulates reactive oxygen species production by phosphorylating gp91phox/NOX2 in human neutrophils Free Radic Biol Med

    Autors : Houssam Raad Hussein Mouawia Hamad Hassan Mohamed El-Seblani Riad Arabi-Derkawi Tarek Boussetta Gougerot-Pocidalo Marie-Anne Dang Pham My-Chan El Benna Jamel

  • Publication date : 11 July 2020 More

    Ferroptosis in Liver Diseases: An Overview Int J Mol Sci

    Autors : Martina Maria Capelletti Manceau Hana Puy Hervé Katell Peoc'h

  • Publication date : 19 June 2020 More

    Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine J Crohns Colitis

    Autors : Al Nabhani Z Berrebi D Martinez-Vinson C Montcuquet N Madre C Roy Maryline Ogier-Denis Eric Dussaillant M Cerf-Bensussan N Zouali H Daniel F Barreau F Hugot Jean-Pierre