Skip to main content

Immunoregulation and Immunopathology

Lucienne Chatenoud & Maria Leite-de-Moraes
Team description

Our team is dedicated to dissecting the intricate cellular and molecular mechanisms underlying immunoregulation and immunopathology. We are particularly interested in harnessing this knowledge to develop innovative biotherapies and biotherapy strategies that can be translated into clinical treatments for conditions such as autoimmunity, allergies, and organ or cell transplantation.

Our research efforts are focused on autoimmune diabetes and the immunopathological mechanisms of asthma, with the aim of improving our understanding and developing novel therapeutic strategies.

Autoimmune Diabetes (Lucienne Chatenoud)

Disease Treatment - We are implementing a Type 1 Diabetes (T1D) prevention trial at Hôpital Necker-Enfants Malades, leveraging a network of diabetology centers in France. Novel therapeutic approaches and combination strategies will be explored using NOD mouse models that we have generated. Our research aims to identify robust efficacy markers for potential use in patients.

Disease Genetics - Our investigations also involve dissecting the cellular and molecular mechanisms related to the Dusp10 mutation, which increases T1D susceptibility in NOD/NckH mice. Our findings suggest that this mutation affects signaling in β-cells, rendering them more vulnerable to immune attacks. Additionally, we are developing a strategy for rapid screening of mutations in NOD mice that influence disease incidence, using non-directed mutagenesis.

Immunopathological Mechanisms of Asthma (Maria Leite-de-Moraes)

We are exploring the potential involvement of ILT cells in the severity of asthma in children. Our research employs an integrated approach, combining clinical phenotype descriptions with the analysis of immune cells, metabolomics, and microbiota from various samples (blood, lung biopsies, and bronchial alveolar lavage) collected from asthmatic and control children in the SevAshtma cohort. This comprehensive approach helps us better understand the immune mechanisms underlying asthma severity.
To gain deeper insights, we conduct in vitro molecular and cellular analyses of specific T cell populations from pediatric patients. In addition, we employ in vivo experimental models, including iNKT-, γδ T-, and MAIT-deficient mice, to dissect the immune mechanisms involved, with a specific focus on ILT cells.

Through these research initiatives, we aim to advance our knowledge of autoimmune diabetes and asthma, ultimately contributing to the development of improved treatments and a better understanding of the underlying immunopathological mechanisms.

Key publications
Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, Gitelman SE, Knecht LA, Niemoeller E, Tian W, Herold KC; PROTECT Study Investigators. Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023; Dec 7;389(23):2151-2161. doi: 10.1056/NEJMoa2308743. PMID: 37861217 .
Chatenoud L, Marquet C, Valette F, Scott L, Quan J, Bu CH, Hildebrand S, Moresco EMY, Bach JF, Beutler B. Modulation of autoimmune diabetes by N-ethyl-N-nitrosourea- induced mutations in non-obese diabetic mice. Dis Model Mech. 2022; Jun 1;15(6):dmm049484. doi: 10.1242/dmm.049484. PMID: 35502705 ; PMCID: PMC9178510.
Foray AP, Candon S, Hildebrand S, Marquet C, Valette F, Pecquet C, Lemoine S, Langa-Vives F, Dumas M, Hu P, Santamaria P, You S, Lyon S, Scott L, Bu CH, Wang T, Xu D, Moresco EMY, Scazzocchio C, Bach JF, Beutler B, Chatenoud L. De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes. Proc Natl Acad Sci U S A. 2021; Nov 23;118(47):e2112032118. doi: 10.1073/pnas.2112032118. PMID: 34782469 ; PMCID: PMC8617500.
Lezmi G, Abou-Taam R, Garcelon N, Dietrich C, Machavoine F, Delacourt C, Adel-Patient K, Leite-de-Moraes M. Evidence for a MAIT-17-high phenotype in children with severe asthma. J Allergy Clin Immunol. 2019; Dec;144(6):1714-1716.e6. doi: 10.1016/j.jaci.2019.08.003. PMID: 31425779 .
Belkadi A, Dietrich C, Machavoine F, Victor JR, Leite-de-Moraes M. γδ T cells amplify Blomia tropicalis-induced allergic airway disease. Allergy. 2019; Feb;74(2):395-398. doi: 10.1111/all.13618. PMID: 30291622 .
Rignault-Bricard R, Machavoine F, Mecheri S, Hermine O, Schneider E, Dy M, Leite-de-Moraes M. IL-3-producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model. Allergy. 2018; Dec;73(12):2342-2351. doi: 10.1111/all.13480. PMID: 29777594 .
Funding and grants