DNA sensing

Microbial DNA can be detected by multiple innate immune receptors and activate inflammatory responses that are essential for the initiation of antimicrobial immunity. In addition to microbial DNA, innate immune receptors can also detect self-DNA released by dying cells. Recognition of self-DNA may aberrantly stimulate immune responses that can lead to inflammatory disorders and autoimmune diseases. On the other hand, self-DNA released by tumors activates inflammatory responses that are required for the development of anti-tumor immunity. We have characterized a novel nuclease called DNASE1L3 that degrades self-DNA released by dying cells and prevents the development of autoimmune syndromes such as lupus. Given the  tolerogenic role of DNASE1L3 in disposing of self-DNA and thus limiting its immunogenicity we are exploring how its function in multiple pathological contexts.

Our projects:

  1. The role of DNASE1L3 in the regulation of tumor-derived DNA immunogenicity.
  1. Function of DNASE1L3 in the pathogenesis of systemic sclerosis.The role of DNASE1L3 in the development of metabolic syndrome and type II diabetes induced by obesity
  1. Function of DNASE1L3 in the pathogenesis of systemic sclerosis.
    Beyond the regulation of self-DNA sensing we have developed projects to investigate the mechanisms that regulate anti-tumor immune responses.
  1. The role of follicular T helper cells in the pathogenesis of Chronic Lymphocytic Leukemia (CLL).
    Dr. Dorothée Duluc leads this project, in collaboration with Dr. Edouard Forcade (clinician at Haut-Lévêque hospital). The goal is to understand the role of follicular helper cells in CLL pathogenesis and particularly their implication in CLL tumor growth.
  1. The role gut-derived T cells in anti-tumor immunity that either occur spontaneously or in response to immunotherapies. This project is developed in collaboration with Dr. Nathalie Schmitt team at Immunoconcept. The goal is to understand how gut microbiota influence anti-tumor immunity induced by immunotherapies. We are hypothesizing that T cells primed in the gut may be recruited to the tumors site and play a crucial role in the induction of anti-tumor immune response.
  1. The impact of aging on spontaneous and immunotherapy induced anti-tumor immune responses.
    This project is developed in collaboration with Dr. David Santamaria and the SIRIC BRIO. The goal is to understand how aging may influence the development of tumors and particularly how aging impact cancer surveillance by the immune system and the efficacy of immunotherapies.

Collaborations

Abroad:

Dr. Boris Reisiz, New York University, New York, USA
Dr. Dipyaman Ganguly, CSIR, Kolkata, India

In France:

Dr. Alexandre Belot, CIRI, and Hospital of Lyon
Dr. Marc Dalod, CIML, Marseille
Dr. Olivier Adotevi, Université Franche Compté
Dr. Lucile Capuron, NeutriNeuro, Bordeaux
Dr. Patrick Blanco, Immunoconcept, Bordeaux
Dr. Thomas Pradeu, Immunoconcept, Bordeaux
Dr. Nathalie Schmittt, Immunoconcept, Bordeaux
Dr. Edouard Forcade, Immunoconcept, Bordeaux
Dr. Maria Mamani Matsuda, Immunoconcept, Bordeaux

Former members:
Anne Garreau – Post Doc 2018-2020

People Involved

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