Role of microglia in neonatal brain injury

Our projects aim to improve understanding of the pathophysiological mechanisms involving microglia in the onset of neurodevelopmental disorders (NDD) and to design innovative therapies. Our current research uses mainly i) animal models of NDD and ii) primary murine microglia or microglia derived from human induced pluripotent stem cells (hiPSCs).

The main projects of this group are:

i) Characterization of sexual dysmorphism, one of the most striking observation in NDD

ii) A detailed understanding of the contributions of microglia, oligodendrocyte and astrocyte subpopulations to the onset of NDD.

iii) Evaluation of the efficacy of neuroprotective strategies, impacting directly or indirectly on developing microglia, astrocytes and oligodendrocytes.

iv) Assessment of the role of DLG4 in immature microglia is also during development, using approaches combining in vitro studies on microglia derived from hiPSCs and primary mouse microglia, as well as in vivo analyses on transgenic mice deficient in Dlg4 in microglia.

v) We are also collaborating with the Neonatology Department of Robert Debré Hospital on the NeoLila project, which aims to better understand and characterize neonatal-specific immune functions, in particular immunosuppression and susceptibility to infection in premature infants.

Membres:
Juliette Van Steenwinckel (Research Engineer), Pierre Gressens (Research Director), Adrien Dufour (Postdoctoral researcher), Camille Hours (PhD student), Olivier Baud (Professor – Hospital Practitioner), Arnaud Bonnard (Professor – Hospital Practitioner), Louise Montalva (Hospital Practitioner – PhD student), Clement Chollat (Associate Professor – Hospital Practitioner), Jennifer Hua (Research Engineer), Amelia Madani (Research Engineer), Leslie Schwendimann (Engineer), Julie Mollet (Engineer), Valérie Faivre (Engineer), Francoise Bergametti (Engineer), Audrey Gibert (Engineer), Éléonore Sizun (Assitant Engineer), Pierrette Young-Ten (Technician), Oliver Bar (Technician), Minh Arnould (Technician).

Recent publications:

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity. Morin C, Faure F, Mollet J, Guenoun D, Heydari-Olya A, Sautet I, Diao S, Faivre V, Pansiot J, Tabet L, Hua J, Schwendimann L, Mokhtari A, Martin-Rosique R, Chadi S, Laforge M, Demené C, Delahaye-Duriez A, Diaz-Heijtz R, Fleiss B, Matrot B, Auger S, Tanter M, Van Steenwinckel J, Gressens P, Bokobza C.. Brain Behav Immun. 2025 Jan;123:824-837. doi: 10.1016/j.bbi.2024.10.023.

Neonatal inflammation impairs developmentally-associated microglia and promotes a highly reactive microglial subset. Dufour A, Heydari Olya A, Foulon S, Réda C, Mokhtari A, Faivre V, Hua J, Bokobza C, Griffiths AD, Nghe P, Gressens P, Delahaye-Duriez A, Van Steenwinckel J. Brain Behav Immun. 2025 Jan;123:466-482. doi: 10.1016/j.bbi.2024.09.019.

Key roles of glial cells in the encephalopathy of prematurity. Van Steenwinckel J, Bokobza C, Laforge M, Shearer IK, Miron VE, Rua R, Matta SM, Hill-Yardin EL, Fleiss B, Gressens P. Glia. 2024 Mar;72(3):475-503. doi: 10.1002/glia.24474.

G protein-coupled receptor 17 is regulated by WNT pathway during oligodendrocyte precursor cell differentiation. Boccazzi M, Macchiarulo G, Lebon S, Janowska J, Le Charpentier T, Faivre V, Hua J, Marangon D, Lecca D, Fumagalli M, Mani S, Abbracchio MP, Gressens P, Schang AL, Van Steenwinckel J. Neurobiol Dis. 2023 Oct 15;187:106315. doi: 10.1016/j.nbd.2023.106315.

Epigenetic priming of immune/inflammatory pathways activation and abnormal activity of cell cycle pathway in a perinatal model of white matter injury. Schang AL, Van Steenwinckel J, Ioannidou ZS, Lipecki J, Rich-Griffin C, Woolley-Allen K, Dyer N, Le Charpentier T, Schäfer P, Fleiss B, Ott S, Sabéran-Djoneidi D, Mezger V, Gressens P.Cell Death Dis. 2022 Dec 13;13(12):1038. doi: 10.1038/s41419-022-05483-4.

A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity. Klein L, Van Steenwinckel J, Fleiss B, Scheuer T, Bührer C, Faivre V, Lemoine S, Blugeon C, Schwendimann L, Csaba Z, Bokobza C, Vousden DA, Lerch JP, Vernon AC, Gressens P, Schmitz T.. Glia. 2022 Sep;70(9):1699-1719. doi: 10.1002/glia.24190. Epub 2022 May 17.

miR-146b Protects the Perinatal Brain against Microglia-Induced Hypomyelination. Bokobza C, Joshi P, Schang AL, Csaba Z, Faivre V, Montané A, Galland A, Benmamar-Badel A, Bosher E, Lebon S, Schwendimann L, Mani S, Dournaud P, Besson V, Fleiss B, Gressens P, Van Steenwinckel J.. Ann Neurol. 2022 Jan;91(1):48-65. doi: 10.1002/ana.26263.

The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation. Boccazzi M, Van Steenwinckel J, Schang AL, Faivre V, Le Charpentier T, Bokobza C, Csaba Z, Verderio C, Fumagalli M, Mani S, Gressens P. Cell Death Dis. 2021 Feb 8;12(2):166. doi: 10.1038/s41419-021-03446-9.