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Nicolas GLAICHENHAUS
Chef d'équipe

L'EQUIPE

Bermudez martin

Blancou

Canaguier

Cremoni

Czerkinsky

Davidovic

Gilet

Glaichenhaus

Hypolite

Khalfallah

Lavergne

Martinuzzi

Pagliano

Panzolini

Pinto barbosa

Sicard

Simon
LES PUBLICATIONS

 
 Paraschivescu C. et al. (2020). Cytokine changes associated with the maternal immune activation (MIA) model of autism: A penalized regression approach. PLoS One

 Taine M. et al. (2020). Does cord blood leptin level mediate the association between neonatal body size and postnatal growth? Results from the EDEN mother-child cohort study. Ann Hum Biol

 Van Dijck A. et al. (2020). Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome. BMC Neurol

 Sicard A. et al. (2020). Donor-specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients. Am J Transplant

 Barbosa S. et al. (2020). Serum cytokines associated with behavior: a cross-sectional study in 5-year-old children. Brain Behav Immun

 Guyot M. et al. (2019). Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes. Nat Biotechnol

CONTACTS
Nicolas GLAICHENHAUS
Chef d'équipe, 04 93 95 77 85

Nadine PAGLIANO
Gestionnaire, 04 93 95 77 17
 

Equipe du Pr Nicolas Glaichenhaus
Systme immunitaire, cerveau et nerfs priphriques

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Activités de l'équipe

Research topics
Since it was established in 1991, our team research efforts have been directed to elucidate the role and the mechanisms of action of immune cell types in infectious diseases, autoimmunity and allergies. In 2014, we have decided to refocus our research on the interactions between the neural and the immune systems.

To investigate how environment perceived by the brain shapes immunity: Immunity is mediated by the activation of immune response genes that encode regulatory and effector molecules such as cytokines, antimicrobial peptides and antibodies. Two types of signals from the body’s internal environment trigger transcriptional activation in innate immune cells: Pathogen-Associated Molecular Patterns (PAMPs) and danger signals derived from cells of the host, stress or death. Growing evidence indicates that neural and endocrine signals form a third class of endogenous stimuli, which are elicited as a result of macro-environmental sensing and modulate immune responses. The resulting neuro–immunological feedback circuit integrates immune responses with other physiological processes to maximize the overall fitness of the organism in response to complex environmental changes caused by microbial, physiological or social–ecological threats. To explore the mechanisms underlying these neuro–immunological feedback circuits, we have established and validated an experimental model of enriched environment (EE) in which mice are exposed to higher levels of cognitive, social and motor stimulation compared to control animals housed in a standard environment (SE). In agreement with previous studies, we have found that EE housing notably improves cognitive abilities, induces resilience to stress and reduces anxiety. Compared to SE mice, we have also found that EE mice are protected from lung metastasis. Protection is associated with lower serum corticosterone levels, increased lung inflammation following extravasation of circulating tumor cells, and rapid killing of early infiltrating tumor cells. Such protection is abolished when inflammatory monocytes are rendered deficient in glucocorticoid receptor signaling. Thus, while inflammatory monocytes have been shown to promote cancer progression, they also have an anti-tumor effect, suggesting that their role is more complex than currently thought. Although the precise mechanisms used by the brain to process environmental stimuli are unknown, our results disclose a novel anti-tumor mechanism whereby glucocorticoid receptor-dependent reprogramming of inflammatory monocytes can inhibit cancer metastasis.

To investigate how peripheral nerves shape immunity: The autonomic nervous system (ANS) is the component of the peripheral nervous system that operates below the level of consciousness and controls visceral functions. It is divided into the para- and the sympathetic nervous systems that use acetylcholine and adrenaline/noradrenaline as their main neurotransmitters respectively. Upon activation, these neurotransmitters are released from postganglionic sympathetic nerve terminals into the periphery. In agreement with a critical role of the ANS in the regulation of immunity, all lymphoid organs exhibit rich sympathetic innervations and most immune cells express functional noradrenaline/adrenaline and Ach receptors. Furthermore, both ANS agonists and antagonists alter immune cell function in vitro and in vivo. It has been established for decades that peripheral nerve electrical stimulation (PNES) could induce the release of neurotransmitters from peripheral nerves. Furthermore, both pre-clinical and clinical studies have demonstrated that Vagus Nerve Stimulation (VNS) could suppress inflammation through molecular and cellular mechanism that have not been entirely elucidated. Building on these data, we have successfully developed mouse models to study the impact of visceral nerve electrical stimulation on immune-mediated inflammatory diseases (IMIDs).

To identify immune-related diagnosis and prognosis biomarkers in psychiatric disorders: Acute or chronic inflammation triggers the release of immune effector molecules (cytokines, chemokines) and immuno-modulatory molecules could access the brain to influence virtually every aspect of brain function and behavior including anorexia, anhedonia, social withdrawal, hyper or hypo-activity and cognitive dysfunction. Furthermore, altered serum cytokine levels have been associated with several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and autism spectrum disorders. Based on these findings, we have made the hypothesis that serum cytokine levels could be relevant diagnosis and prognosis biomarkers in psychiatric patients. To validate this hypothesis, we are taken advantage of clinical data and serum samples that have been collected within the frame of several cohorts of psychiatric patients. Analyzing serum samples for the levels of several immune-related molecules allowed us to identify serum biomarkers that could predict response to treatment in a subset of first-episode psychosis patients. Likewise, we have successfully identified serum biomarkers that discriminated patients with bipolar and unipolar disorders. Further validation of our results in future clinical trials would pave the way for the development of a blood-based assisted clinical decision support system for patients with major affective and psychotic disorders. 

To elucidate how the gut microbiota regulates brain functions in mice: The intestinal microbiota plays a key role in host homeostasis by regulating intestinal barrier function, metabolism, immune responses and behavior. Acute or chronic stress, either in early life or adulthood, modifies the microbiome and predisposes to a number of psychiatric disorders: schizophrenia, major depressive disorder, anxiety disorders and autism spectrum disorders. Those disorders can also be associated with microbiota dysbiosis and chronic low-grade inflammation. Such associations are also observed in mice exposed to environmental stress such as maternal immune activation (MIA). In the MIA model, microbiota dysbiosis, altered intestinal permeability, local inflammation are accompanied by behavioral impairments. We have made the hypothesis that disruption of the gut-brain axis and more specifically that specific gut bacterial species impact behavior and gastrointestinal functions via the production of bacteria-derived metabolites. We are currently investigating the role of specific bacterial species and associated metabolites in several dimensions of the host’s behavior in the MIA model.
 

Researchers
  • Nicolas Glaichenhaus, Professor at the Université Nice Sophia Antipolis
  • Evelyne Mougneau, Maître de Conférences at the Université Nice Sophia Antipolis
  • Philippe Blancou, Maître de Conférences at the Université Nice Sophia Antipolis, joined in September 2013
  • Cécil Czerkinsky, INSERM research director (DR2), joined in April 2014
  • Emanuela Martinuzzi, INSERM researcher (CDI), joined in September 2015
  • Laetitia Davidovic, CNRS researcher (CR1), joined in September 2015
  • Olfa Khalfallah, INSERM researcher (CR1), joined in October 2016
  • Thomas Simon, postdoctoral fellow, joined the team in August 2017
  • Susana Barbosa, postdoctoral fellow, joined the team in March 2017
 
PhD students
  • Aidan Falvey, joined the team in November 2015, supported by Signalife Labex fellowship;
  • Cristina Paraschivescu, joined the team in September 2016, supported by a Signalife Labex fellowship
  • Patricia Bermudez-Martin, joined the team in September 2015 as IE, started PhD in March 2018
 
Engineers and technicians
  • Clara Panzolini, joined the team in February 2017

Financements

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IPMC UMR7275
660 Route des Lucioles
SOPHIA ANTIPOLIS
06560 VALBONNE

tél : 04 93 95 77 77 - fax : 04 93 95 77 08

 

INSTITUT DE PHARMACOLOGIE MOLECULAIRE ET CELLULAIRE

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