Neuroimmunology

PROFILE

Emerging evidence shows the existence of diverse physical and functional interactions between the immune and nervous systems. The nervous system may regulate the immune response and its potency against viral and bacterial infections and tumour development. Similarly, the immune system appears to be able to regulate some functions of the nervous system including processes involved in behavior, learning and memory. Due to the existence of this bidirectional cross-talk between these two systems, the deregulation of neuro-immune communications could result in immune-related diseases or in neurological/psychiatric associated disorders. The primary aim of our research is to understand the mechanisms operating in neuro-immune communications and thus to determine how stimulation of some pathways in the nervous system may potentiate or inhibit immune responses during infectious diseases, cancer and autoimmunity. We also aim to understand how the activity of specific immunological components may regulate some cognitive tasks or contribute in the physiopathologic scenario of neurodegenerative disorders.

LAB MEMBERS

Research Head: Rodrigo Pacheco

Postdoctoral Fellows: Carolina Prado

Doctoral students: Daniela Elgueta • Javier Campos • Andro Montoya

Undergraduate students: Nicole Rivera • Vania Macias

Research Assistants: Valentina Ugalde • Francisco Osorio-Barrios • María Alexandra Espinoza

COLLABORATIONS

National Collaborations:
• Dr. Alvaro Lladser (Fundación Ciencia & Vida). We are studying how the dopaminergic regulation of cytotoxic T lymphocytes and dendritic cells affects the adaptive immune response against melanoma.
• Dr. Jimmy Stehberg and Dr. Lorena Varela (Faculty of Biological Sciences, UNAB). We are studying how dopaminergic regulation of T cells affects the development of neurogenesis in the hippocampus.
• Dr. Andrea Soza and Alfonso González (Faculty of Biological Sciences- Catholic University). We are studying how galectin-8 affects the physiology of T-cells in the context of autoimmunity.
• Dr. María Rosa Bono and Dr. Daniela Sauma (Faculty of Science, Universidad de Chile). We are studying the role of CD39 and CD73 in the acquisition of inflammatory and suppressive functional phenotypes of CD4+ T-cells.
• Dr. Soledad Matus (Faculty of Medicine, Universidad de Chile). We are analyzing the role of the dopaminergic regulation of CD4+ T-cells in the development of amyotrophic lateral sclerosis.
• Dr. Luis Michea (Faculty of Medicine, Universidad de Chile). We are studying how dendritic cells and neutrophils contribute to the development and progression of hypertension.

International Collaborations:
• Dr. Rafael Franco (Universidad de Barcelona, Barcelona, España), Dr. Marisol Aymerich (Universidad de Navarra, Pamplona, España) and Dr. Roque Villagra (Universidad de Chile, Santiago, Chile). We are studying the therapeutic potential of dopamine receptor inhibition in T-cell as a treatment for Parkinson’s disease.
• Dr. Vanesa Sánchez-Guajardo (Aarhus University, Aarhus, Denmark). We are analyzing the dopaminergic regulation of CD4+ T-cells against alpha-synuclein associated to Parkinson’s disease.
• Rafael Franco (Universidad de Barcelona, Barcelona, España). We are studying the role of G-protein-coupled receptor heteromers as immune system sensors.
• Marco Cosentino (University of Insubria, Varese, Italy). We are studying how dopamine receptors expressed on dendritic cells participate in the development and progression of Multiple Sclerosis.

SELECTED PUBLICATIONS

  • Doñas C., Carrasco M., Fritz M., Prado C., Tejón G., Osorio-Barrios F., Manríquez V., Pacheco R., Reyes P., Bono M. R., Loyola A., Rosemblatt M. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on dendritic cells. J. Autoimmun. 75:105-117. doi: 10.1016/j.jaut.2016.07.011 (2016). | | ABSTRACT
  • Elgueta D., Aymerich M. S., Contreras F., Montoya A., Celorrio M., Rojo-Bustamante E., Riquelme E., González H., Vásquez M., Franco R., Pacheco R. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease. Neuropharmacology 113:110-123 (2017) | | ABSTRACT
  • Figueroa C., Gálvez-Cancino F., Oyarce C., Contreras F., Prado C., Valeria C., Cruz S., Lladser A., Pacheco R. Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity. J. Neuroimmunol. 303:99-107 (2017) | | ABSTRACT
  • Pacheco R. Targeting dopamine receptor D3 signalling in inflammation. Oncotarget 8(5):7224-7225 (2017) | | ABSTRACT
  • Contreras F., Prado C., González H., Franz D., Osorio-Barrios F., Osorio F., Ugalde V., Lopez E., Elgueta D., Figueroa A., Lladser A., Pacheco R. Dopamine receptor D3 signaling on CD4+ T cells favors Th1- and Th17-mediated immunity. J. Immunol. 196(10):4143 (2016) | | ABSTRACT
  • Fernández D., Flores-Santibáñez F., Neira J., Osorio F., Tejón G., Núñez S., Hidalgo Y., Fuenzalida M. J., Meza D., Ureta G., Lladser A., Pacheco R., Acuña-Castillo C., Guixé V., Quintana F. J., Bono M. R., Rosemblatt M., Sauma D. Purinergic signaling as a regulator of Th17 cell plasticity. PloS ONE 11(6): e0157889 (2016) | | ABSTRACT
  • Moraga-Amaro R., González H., Ugalde V., Donoso-Ramos J. P., Quintana-Donoso D., Lara M., Morales B., Rojas P., Pacheco R., Stehberg J. Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory. Neuropharmacol. 103: 222-235 (2016) | | ABSTRACT
  • Oliva H., Pacheco R., Rodríguez-García M., Naranjo-Gómez M., Climent N., Martínez-Navio J. M., Gil C., Plana M., García F., Miró J. M., Franco R., Borras F., Navaratnam N., Gatell J. M., Gallart T. Increased expression with differential subcellular location of cytidine deaminase APOBEC3G in human CD4+ T-cell activation and dendritic cell maturation. Immunol. Cell Biol. doi: 10.1038/icb.2016.28 (2016) | | ABSTRACT
  • González H., Contreras F., Pacheco R. Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells. J. Neuroimmune Pharmacol. 10(4): 561-575 (2015) | | ABSTRACT
  • Franz D., Contreras F., González H., Prado C., Elgueta D., Figueroa C., Pacheco R. Dopamine receptors D3 and D5 regulate CD4 +T-cell activation and differentiation by modulating ERK activation and cAMP production. J. Neuroimmunol. 284: 18-29 (2015) | | ABSTRACT
  • González H., Pacheco R. T-cell mediated regulation of neuroinflammation involved in neurodegenerative diseases. J. Neuroinflammation 11(1): 201 (2014) | | ABSTRACT
  • Fernández-Suárez D., Celorrio M., Riezu-Boj J. I., Pacheco R., González H., Hillard C. J., Franco R., Aymerich M. S. Neuroprotective effect of the monoacylglycerol lipase inhibitor JZL184 in a chronic MPTP mouse model. Neurobiol. Aging 35(11): 2603-2616 (2014) | | ABSTRACT
  • Moraga-Amaro R., González H., Pacheco R., Stehberg J. Dopamine receptor D3 deficiency results in chronic depression and anxiety. Behav. Brain Res. 274(1): 186-193 (2014) | | ABSTRACT
  • González H., Elgueta D., Montoya A., Pacheco R. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J. Neuroimmunol. 274(1-2): 1-13 (2014)| | | ABSTRACT
  • Pacheco R., Contreras F. and Zouali M. The dopaminergic system in autoimmune diseases. Frontiers in Immunology. 5: 117. (2014) | PDF | ABSTRACT
  • González H., Contreras F., Prado C., Elgueta D., Franz D., Bernales S. and Pacheco R. Dopamine receptor D3 expressed on CD4+ T-cells favours neurodegeneration of dopaminergic neurons during Parkinson's disease. Journal of Immunology. 190(10):5048-5056. (2013) | PDF | ABSTRACT
  • Prado C., Bernales S. and Pacheco R. Modulation of T-cell mediated immunity by dopamine receptor D5. Endocrine, Metabolic & Immune Disorders-Drug Target. 13(2):184-194. (2013) | PDF | ABSTRACT
  • Prado C., Contreras F., González H., Díaz P., Elgueta D., Barrientos M., Herrada A. A., Lladser À., Bernales S. and Pacheco R. Immunity on Dendritic Cells Potentiates Th17-Mediated Stimulation of Dopamine Receptor D5 Expressed. J. Immunol. 188, 3062-3070 (2012) | PDF | ABSTRACT
  • Martinez-Navio J. M., Casanova V., Pacheco R., Naval-Macabuhay I., Climent N., Garcia F., Gatell J. M., Mallol J., Gallart T., Lluis C. and Franco R. Adenosine deaminase potentiates the generation of effector, memory and regulatory CD4+ T-cells. J. Leukoc. Biol. 89 (1): 127-136 (2011) | PDF | ABSTRACT
  • Pacheco R., Prado C. E., Barrientos M. J., Bernales S. Role of dopamine in the physiology of T-cells and dendritic cells. J. Neuroimmunol. 216 (1-2): 8-19 (2009) | PDF | ABSTRACT
  • Carreño L. J., Pacheco R., Gutierrez M. A., Jacobelli S., Kalergis A. M. Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fcᵞ receptors and costimulatory molecules on dendritic cells. Immunology 128 (3): 334-341 (2009) | PDF | ABSTRACT
  • Martinez-Navio J. M., Climent N., Pacheco R., Garcia F., Plana M., Nomdedeu M., Oliva H., Rovira C., Miralles L., Gatell J. M., Gallart T., Mallol J., Lluis C. and Franco R. Immunological Dysfunction in HIV-1-Infected Individuals caused by Impairment of adenosine deaminase-induced costimulation of T-Cell activation. Immunology 128 (3): 393-404 (2009) | PDF | ABSTRACT
  • Herrada A. A., Contreras F. J., Tobar J. A., Pacheco R. and Kalergis A. M. Immune complex-induced enhancement of bacterial antigen presentation requires FcУ Receptor III expression on dendritic cells. PNAS 104 (33): 13402-13407 (2007) | PDF | ABSTRACT
  • Franco R., Pacheco R., Lluis C., Ahern G. P. and O’Connell P. J. The emergence of neurotransmitters as immune modulators. Trends Immunol. 28 (9): 400-407 (2007) | PDF | ABSTRACT
  • Pacheco R., Gallart T., Lluis C. and Franco R. Role of glutamate on T-cell mediated immunity. J. Neuroimmunol. 185 (1-2): 09-19 (2007) | PDF | ABSTRACT