Projects per year
Inappropriate CNS immune cell reactions often underpin neurological illnesses. Thus, their underlying cellular and molecular mechanisms have emerged as a potential therapeutic target. The Neuro-Immunology Group aims to identify the immunological properties of CNS immune cells, with microglia representing the key effector cells, as well as to investigate their crosstalk with peripheral immune cells under tumorigenic, inflammatory and neurodegenerative conditions in order to identify specific programs which could represent targets for therapeutic intervention.
The group consistently achieves these goals through three steps:
1. Characterise cells at the -omics level, for instance elucidating their epigenetic, transcriptional and metabolic signatures;
2. Identify genes and pathways that are perturbed under disease conditions and compare them to homeostatic states;
3. Investigate how manipulating the identified pathways affects the acquired phenotype and eventually the disease outcome.
To reach these objectives, the group takes advantage of valuable biological samples from patients and specific mouse models for human brain tumours and neurodegenerative diseases as well as in vitro eukaryotic cell cultures. They combine -omics analyses with specific molecular biology tools and cutting-edge biochemical assays. Additionally, they work in close collaboration with bioinformaticians and computational biologists to infer the underlying networks as well as to integrate their data with existing information gathered through literature review.
On top of this systems approach, much of their attention is focused on IRG1/ACOD1, a key immune response gene expressed by myeloid cells under inflammatory, tumorigenic and neurodegenerative conditions. They have previously elucidated the function of IRG1/ACOD1 protein by demonstrating that it links metabolism to immunity by catalysing the production of the anti-microbial/anti-inflammatory metabolite itaconate from cis-aconitate in the tricarboxylic acid (TCA) cycle. Notably, their discovery contributed to pave the way to the emerging field of immunometabolism, which is currently revealing the crucial role of metabolic reprogramming in immune responses.
A better understanding of the cellular and molecular mechanisms underlying the immunological properties of CNS immune cells and the subsequent ability to manipulate them, such as render them anti-tumorigenic or neuroprotective, will pave the way to novel therapeutic applications tailored to specific neurological diseases with an immunological component.
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I2TRON Frida Lind-Holm Mogensen: Microglia programs under PARK7/DJ-1 deficiency, a genetic cause of Parkinson’s disease
Michelucci, A. & Lind-Holm, F.
15/02/21 → 14/02/25
Michelucci, A., Skupin, A. & Betsou, F.
1/01/21 → 31/12/22
Allergic airway inflammation delays glioblastoma progression and reinvigorates systemic and local immunity in micePoli, A., Oudin, A., Muller, A., Salvato, I., Scafidi, A., Hunewald, O., Domingues, O., Nazarov, P. V., Puard, V., Baus, V., Azuaje, F., Dittmar, G., Zimmer, J., Michel, T., Michelucci, A., Niclou, S. P. & Ollert, M., 9 Oct 2022, (E-pub ahead of print) In: Allergy: European Journal of Allergy and Clinical Immunology.
Research output: Contribution to journal › Article › Research › peer-reviewOpen Access
AllergoOncology: Danger signals in allergology and oncology: A European Academy of Allergy and Clinical Immunology (EAACI) Position PaperBergmann, C., Poli, A., Agache, I., Bianchini, R., Bax, H. J., Castells, M., Crescioli, S., Dombrowicz, D., Ferastraoaru, D., Fiebiger, E., Gould, H. J., Hartmann, K., Izquierdo, E., Jordakieva, G., Josephs, D. H., Jutel, M., Levi-Schaffer, F., de las Vecillas, L., Lotze, M. T., Osborn, G., & 11 others, Sep 2022, In: Allergy: European Journal of Allergy and Clinical Immunology. 77, 9, p. 2594-2617 24 p.
Research output: Contribution to journal › Article › Research › peer-reviewOpen Access2 Citations (Scopus)
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolismChen, F., Elgaher, W. A. M., Winterhoff, M., Büssow, K., Waqas, F. H., Graner, E., Pires-Afonso, Y., Casares Perez, L., de la Vega, L., Sahini, N., Czichon, L., Zobl, W., Zillinger, T., Shehata, M., Pleschka, S., Bähre, H., Falk, C., Michelucci, A., Schuchardt, S., Blankenfeldt, W., & 2 others, May 2022, In: Nature Metabolism. 4, 5, p. 534-546 13 p.
Research output: Contribution to journal › Article › Research › peer-reviewOpen Access5 Citations (Scopus)