Neuroimmuno-Repair

Neuroinmuno-Reparación

Neuroimmuno-Repair

 

Principal investigator: Diego Clemente López, PhD.
E-mail: dclemente@sesacm.jccm.es

 

The Group of Neuro Immuno-Repair (GNIR) studies the nervous system - immune system relationship in the context of demyelinating diseases, specifically in multiple sclerosis. Demyelinating lesions of the central nervous system displayed by MS patients show different degrees of histopathological evolution, which in turn is matched by a different capacity for spontaneous remyelination (i.e. neural repair). The transition from the destructive to the repair phase of the disease involves several types of regulatory cells that modulate the immune response, thus allowing oligodendrocyte precursors to remyelinate naked axons. Among the regulatory cells, our group is focused on myeloid-derived suppressor cells (MDSCs) and follows three lines of research:

1. Application of MDSCs as accelerating agents in the transition from tissue destruction to neuro-repair, either directly or after ex vivo pharmacological potentiation of these cells.
2. Use of MDSCs as biomarkers of MS aggressiveness, taking into consideration both the clinical course and the degree of tissue destruction associated with the pathology.
3. Direct neuro-regenerative function of MDSCs through the proliferation, migration, differentiation or survival of oligodendrocyte precursors, or via the preservation of mature myelinating oligodendrocytes. 

 

To study all these processes, our group employs in vitro cell cultures of oligodendrocytes and their precursors, T-lymphocytes and MDSCs (either as individual cultures or co-cultures),  as well as ex vivo organotypic cerebellar cultures in which we study spontaneous remyelination after experimental demyelination. We also use the mouse model of MS, i.e. experimental autoimmune encephalomyelitis (EAE). Furthermore, we have access to samples from MS patients and control subjects, for in vivo study of the MDSC distribution and function.

 

Our group collaborates with various national and international groups and is a member  of the Spanish Network of Multiple Sclerosis and the European platform "nEUROinflammation".

 

 

 

Selected publications 

 

- Melero-Jerez C, Ortega MC, Moliné-Velázquez V, Clemente D. Myeloid derived suppressor cells in inflammatory conditions of the central nervous system. Biochim Biophys Acta-Mol Basis Dis. 2015; 3: 368-380. doi: 10.1016/j.bbadis.2015.10.015.  

 

- Moline-Velazquez V, Ortega MC, Vila-del Sol V, Melero-Jerez C, de Castro F, Clemente D. The synthetic retinoid Am80 delays recovery in a model of multiple sclerosis by modulating myeloid-derived suppressor cell fate and viability. Neurobiol Dis. 2014; 67: 149-164. doi: 10.1016/j.nbd.2014.03.017. 

 

- Ortega MC, Cases O, Merchán P,  Kozyraki R, Clemente D.* de Castro F*. *These authors equally contributed to this work. Megalin mediates the influence of Sonic Hedgehog on oligodendrocyte precursor cell migration and proliferation during development.Glia. 2012; 60:851–866. doi: 10.1002/glia.22316. 

 

- Clemente D, Ortega MC, Arenzana FJ, de Castro F.FGF-2 and Anosmin-1 are selectively expressed in different types of multiple sclerosis lesions. J. Neurosci. 2011; 31:14899-14909. doi: 10.1523/JNEUROSCI.1158-11.2011. 

 

- Moliné-Velázquez V, Cuervo H, Vila-del Sol V, Ortega MC, Clemente D1*, de Castro F*. *These authors equally contributed to this work. 1Corresponding author. Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis. “Cover page” seleccionada para el volumen 21. Brain Pathol. 2011; 21: 678-691. doi: 10.1111/j.1750-3639.2011.00495.x.

 

 

 

Patents

 

Method for predicting the histopathological features of the lesions in a subject with a demyelinating disease of the central nervous system.
INVENTORS: de Castro, F., Clemente, D., Ortega, M.C., y Arenzana, F.J.
INTELECTUAL PROPERTY HOLDER: FUHNPAIIN
SPANISH PATENT Registration Nº:P200930661 
INTERNATIONAL PATENT Registration Nº: PCT/ES2010/070584;Countries: EU, CAN, JPN, AUS

 

Biomarker for the histopathological classification of the lesions in a subject with demyelinating disease of the central nervous system.
INVENTORS: de Castro, F., Clemente, D., Ortega, M.C., y Arenzana, F.J.
INTELECTUAL PROPERTY HOLDER: FUHNPAIIN
SPANISH PATENT Registration Nº: P201030090
INTERNATIONAL PATENT Registration Nº PCT/ES2010/070584; Countries: EU, CAN, JPN, AUS

 

 

 

Personnel
 

Diego Clemente López: Laboratory chief; PhD. in Biology

 

Carolina Melero Jerez: Predoctoral researcher; MSc. in Neurocience

 

Isabel Machin Diaz: Laboratory manager; BSc. in Food Technology

 

Rafael Lebron Galán: Laboratory technician

 

 

 

Ongoing projects

 

Myeloid-derived suppressor cells as novel biomarkers of the multiple sclerosis: the relation with tissue damage and neuro-repair.
PI: Diego Clemente López; Funded by the Health Research Fund, Instituto de Salud Carlos III (ISCIII), Ministry of Economy and Competitiveness (2016-2018).

 

Initial Training Network “nEUROinflammation”.
PI: Diego Clemente López; Funded by  Marie Curie Actions, FP7, European Union (2014-2017).

 

Glunomab-driven enhancing of MDSCs.
PI: Diego Clemente López; Funded by PAION GmbH  (2014-2016). 

 

Spanish Network for Multiple Sclerosis-REEM (thematic program networks for cooperative research- RETICS, ISCIII).
PI: Fernando de Castro Soubriet. Funded by  Health Research Fund -ISCIII (2013-2016).

 

 

 

Research lines

 

- Histopathological analysis of the inflammatory lesion environment produced by multiple sclerosis.

 

- Screening for molecular and cellular biomarkers of multiple sclerosis severity.

 

- Study of myeloid-derived suppressor cells as potentiating agents of neuralrepair.

 

- Identification of new therapeutic targets for neuroprotection in multiple sclerosis and other diseases of the central nervous system.