Researh & development

Autoimmunity

Profile

The gut microbiota, a wide variety of commensals microorganisms colonizing the gastrointestinal tract, coexist in symbiosis with the host even though immune cells are constantly in contact with microbial antigens at the mucosal surfaces. The gut microbiota produces various metabolites from exogenous components of the diet and/or endogenous compounds generated by microorganisms and the host, keys for the normal development of immunity and homeostasis of the individual. Therefore, changes in the gut microbial community composition are thought to contribute to metabolic and immune-mediated diseases. Short-chain fatty acids (SCFAs) constitute the most abundant in metabolites derived from the intestinal microbiota and has been described its involvement in bidirectional communication between the brain and the intestine. Our group is currently studying how these metabolites affects the development of autoimmune diseases of the nervous system central. Currently, we are focused on deciphering how the SCFAs modulate the function of colonic T lymphocytes and innate lymphoid cells (ILCs) and its effect in a murine model of sclerosis multiple.

+5623672052

cprado@cienciavida.org

Research Head: Carolina Prado Terrazas

Undergraduate Students: Daniela Muñoz, Joaquín Muñoz

National Collaborations

  • Dr. Luis Michea (University of Chile)
  • Dr. Cristian Amador (Central University)
  • Dr. Isabel Yuseff (Pontificia Universidad Católica de Chile)
  • Dr. Fabiola Osorio (University of Chile)

Publications

Brücher R, Cifuentes M, Acuña MJ, Albala C, Rojas CV. “Larger anti-adipogenic effect of angiotensin II on omental preadipose cells of obese humans”. Obesity 15: 1643-1646, 2007.

Fuentes P, Acuña MJ, Cifuentes M, Rojas CV. “The anti-adipogenic effect of angiotensin II on human preadipose cells involves ERK1,2 activation and PPARG phosphorylation”. J Endocrinol. 206:75-83, 2010.

Fernández M, Acuña MJ, Reyes M, Olivares D, Hirsch S, Bunout D, de la Maza MP. “Proliferation and differentiation of human adipocyte precursor cells: differences between the preperitoneal and subcutaneous compartments”. J Cell Biochem. 111:659-64, 2010.

Cabello-Verrugio C, Acuña MJ, Morales MG, Becerra A, Simon F, Brandan E. “Fibrotic response induced by angiotensin-II requires NAD(P)H oxidase-induced reactive oxygen species (ROS) in skeletal muscle cells”. Biochem Biophys Res Commun.410:665-70, 2011.

Cabello-Verrugio C, Santander C, Cofré C, Acuña MJ, Melo F, Brandan E. “The internal region leucine-rich repeat 6 of decorin interacts with low density lipoprotein receptor- related protein-1, modulates transforming growth factor (TGF)-β-dependent signaling, and inhibits TGF-β-dependent fibrotic response in skeletal muscles”. J Biol Chem 287:6773-87, 2012.

Morales MG, Vazquez Y, Acuña MJ, Rivera JC, Simon F, Salas JD, Alvarez Ruf J, Brandan E, Cabello-Verrugio C. “Angiotensin II-induced pro-fibrotic effects require p38MAPK activity and transforming growth factor beta 1 expression in skeletal muscle cells”. Int J Biochem Cell Biol. 11:1993-2002, 2012.

Painemal P, Acuña MJ, Riquelme C, Brandan E, Cabello-Verrugio C.“Transforming growth factor type beta 1 increases the expression of angiotensin II receptor type 2 by a SMAD- and p38 MAPK-dependent mechanism in skeletal muscle”. Biofactors. 39(4):467-75, 2013.

Riquelme C*, Acuña MJ*, Torrejón J, Rebolledo D, Cabrera D, Santos RA, Brandan E.“ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis”. PLoS One. 9(4):e93449, 2014. *Estos autores contribuyeron de igual manera al desarrollo de este trabajo.

Acuña MJ, Pessina P, Olguin H, Cabrera D, Vio CP, Bader M, Muñoz-Canoves P, Santos RA, Cabello-Verrugio C, Brandan E. “Restoration of muscle strength in dystrophic muscle by angiotensin-1-7 through inhibition of TGF-β signalling”. Hum Mol Genet. 23(5):1237-49, 2014.

Bueno SM, González PA, Pacheco R, Leiva ED, Cautivo KM, Tobar HE, Mora JE, Prado CE, Zúñiga JP, Jiménez J, Riedel CA, Kalergis AM. Host immunity during RSV pathogenesis. Int Immunopharmacol. 2008 Oct; 8(10):1320-9.

González PA, Prado CE, Leiva ED, Carreño LJ, Bueno SM, Riedel CA, Kalergis AM. Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells. Proc Natl Acad Sci USA. 2008 Sep 30; 105(39):14999-5004.

Pacheco R, Prado CE, Barrientos MJ, Bernales S. Role of dopamine in the physiology of Tcells and dendritic cells. J Neuroimmunol. 2009 Nov 30; 216(1-2):8-19.

Prado C, Contreras F, González H, Díaz P, Elgueta D, Barrientos M, Herrada AA, Lladser Á, Bernales S, Pacheco R. Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol. 2012 Apr 1; 188(7): 3062-70. 2009

Gonzalez H, Contreras F, Prado CE, Elgueta D, Franz D, Bernales S, Pacheco R. Dopamine receptor D3 expressed on CD4+ T-cells favours neurodegeneration of dopaminergic neurons during Parkinson’s disease. J Immunol, 2013 May 15; 190(10):5048-56. 2012

Prado C, Bernales S, Pacheco R. Modulation of T-cell mediated immunity by dopamine receptor D5. Endocr Metab Immune Disord Drug Targets. 2013 Jun; 13(2):184-94.

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. 2015 Jul 15;284:18-29

Gómez R; Ramírez B; Cespedes P; Cautivo K; Riquelme S; Prado C; Gonzalez, P; Kalergis A.Contribution of Fcγ Receptors to Human Respiratory Syncytial Virus Pathogenesis and the Impairment of T cell Activation by Dendritic Cells. Immunol. 2016 Jan; 147(1):55-72

Oliva H, Pacheco R, Martinez-Navio JM, Rodríguez-García M, Naranjo-Gómez M, Climent N, Prado C, Gil C, Plana M, García F, Miró JM, Franco R, Borras FE, Navaratnam N, Gatell JM, 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. 2016 Aug;94(7):689-700.

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. 2016 May 15; 196(10):4143-9.

Doñas C, Carrasco M, Fritz M, Prado C, Tejón G, Osorio-Barrios F, Manríquez V, Pacheco R, Reyes P, Bono MR, Loyola A, Rosemblatt M. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs. J Autoimmun. 2016; 75:105-117.

Figueroa C, Gálvez-Cancino F, Oyarce C, Contreras F, Prado C, Valeria C, Cruz S, Lladser A, Pacheco. Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity. J Neuroimmunol. 2017 Feb 15; 303:99-107.

Hevia D, Araos P, Prado C, Fuentes Luppichini E, Rojas M, Alzamora R, Cifuentes-Araneda F, Gonzalez AA, Amador CA, Pacheco R, Michea L. MyeloidCD11c+ Antigen-Presenting Cells Ablation Prevents Hypertension in Response to Angiotensin II Plus High-Salt Diet. Hypertension. 2018 Apr; 71(4):709- 718.

Prado C, Gaiazzi M, González H, Ugalde V, Figueroa A, Osorio-Barrios FJ, López E, Lladser A, Rasini E, Marino F, Zaffaroni M, Cosentino M, Pacheco R. Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis. Front Immunol. 2018 Mar 21; 9:571

Prado C, Iruretagoyena M, Burgos PI, Pacheco R. Smoking promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients. Rev Med Chil. 2018 Feb; 146(2):150-159.

Osorio-Barrios F, Prado C, Contreras F, Pacheco R. Dopamine Receptor D5 Signaling Plays a Dual Role in Experimental Autoimmune Encephalomyelitis Potentiating Th17-Mediated Immunity and Favoring Suppressive Activity of Regulatory T-Cells. Front Cell. Neurosci. 2018 Jul 10; 12:192.

Araos P*, Prado* C, Lozano M, Figueroa S, Espinoza A, Berger T, Mak TW, Jaisser F, Pacheco R, Michea L, Amador CA. Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation. J Hypertens. 2019 Feb 12. doi: 10.1097/HJH.0000000000002067.

Elgueta D, Contreras F, Prado C, Montoya A, Ugalde V, Chovar O, Villagra R, Henríquez C, Abellanas M, Aymerich M, Franco R, Pacheco R. Dopamine Receptor D3 Expression Is Altered in CD4+ T-Cells From Parkinson’s Disease Patients and Its Pharmacologic Inhibition Attenuates the Motor Impairment in a Mouse Model. Front. Immunol.,01 May 2019. doi.org/10.3389/fimmu.2019.00981

Prado C, Ugalde V, González H, Figueroa A, López E, Lladser A, Pacheco R. STAT3 Activation in Combination with NF-KappaB Inhibition Induces Tolerogenic Dendritic Cells with High Therapeutic Potential to Attenuate Collagen-Induced Arthritis. J Immunol Res. 2019 Jul 1;2019:1982570. doi: 10.1155/2019/1982570.

Ugalde V, Contreras F, Prado C, Chovar O, Espinoza A, Pacheco R. Dopaminergic signaling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation. Mucosal Immunol. 2020 Nov 12. doi:10.1038/s41358-020-00354-7. Epub ahead of print. PMID: 33184477

Doñas C, Neira J, Osorio-Barrios F, Carrasco M, Fernández D, Prado C, Loyola A, Pacheco R, Rosemblatt M. The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells. Sci Rep. 2021 Jan 14;11(1):1342. doi: 10.1038/s41598-020-79122-3.

Osorio-Barrios F, Navarro G, Campos J, Ugalde V, Prado C, Raïch I, Contreras F, López E, Espinoza A, Lladser A, Franco R, Pacheco R. The Heteromeric Complex Formed by Dopamine Receptor D 5 and CCR9 Leads the Gut Homing of CD4 + T Cells Upon Inflammation. Cell Mol Gastroenterol Hepatol. 2021;12(2):489-506. doi: 10.1016/j.jcmgh.2021.04.006. Epub 2021 Apr 20.

Ugalde V, Contreras F, Prado C, Chovar O, Espinoza A, Pacheco R. Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation. Mucosal Immunol. 2021 May;14(3):652-666. doi: 10.1038/s41385-020-00354-7. Epub 2020 Nov 12. PMID: 33184477

Prado C, Osorio-Barrios F, Falcón P, Espinoza A, Saez JJ, Yuseff MI, Pacheco R. Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity. J Neuroinflammation. 2021 Dec 17;18(1):292. doi: 10.1186/s12974-021-02338-1. PMID: 34920747

Other publications

Prado C, Osorio-Barrios F, Falcón P, Espinoza A, Saez JJ, Yuseff MI, Pacheco R. Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity. J Neuroinflammation. 2021 Dec 17;18(1):292. doi: 10.1186/s12974-021-02338-1. PMID: 34920747

Ugalde V, Contreras F, Prado C, Chovar O, Espinoza A, Pacheco R. Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation. Mucosal Immunol. 2021 May;14(3):652-666. doi: 10.1038/s41385-020-00354-7. Epub 2020 Nov 12. PMID: 33184477

Osorio-Barrios F, Navarro G, Campos J, Ugalde V, Prado C, Raïch I, Contreras F, López E, Espinoza A, Lladser A, Franco R, Pacheco R. The Heteromeric Complex Formed by Dopamine Receptor D 5 and CCR9 Leads the Gut Homing of CD4 + T Cells Upon Inflammation. Cell Mol Gastroenterol Hepatol. 2021;12(2):489-506. doi: 10.1016/j.jcmgh.2021.04.006. Epub 2021 Apr 20.

Doñas C, Neira J, Osorio-Barrios F, Carrasco M, Fernández D, Prado C, Loyola A, Pacheco R, Rosemblatt M. The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells. Sci Rep. 2021 Jan 14;11(1):1342. doi: 10.1038/s41598-020-79122-3.

Ugalde V, Contreras F, Prado C, Chovar O, Espinoza A, Pacheco R. Dopaminergic signaling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation. Mucosal Immunol. 2020 Nov 12. doi:10.1038/s41358-020-00354-7. Epub ahead of print. PMID: 33184477

Prado C, Ugalde V, González H, Figueroa A, López E, Lladser A, Pacheco R. STAT3 Activation in Combination with NF-KappaB Inhibition Induces Tolerogenic Dendritic Cells with High Therapeutic Potential to Attenuate Collagen-Induced Arthritis. J Immunol Res. 2019 Jul 1;2019:1982570. doi: 10.1155/2019/1982570.

Elgueta D, Contreras F, Prado C, Montoya A, Ugalde V, Chovar O, Villagra R, Henríquez C, Abellanas M, Aymerich M, Franco R, Pacheco R. Dopamine Receptor D3 Expression Is Altered in CD4+ T-Cells From Parkinson’s Disease Patients and Its Pharmacologic Inhibition Attenuates the Motor Impairment in a Mouse Model. Front. Immunol.,01 May 2019. doi.org/10.3389/fimmu.2019.00981

Araos P*, Prado* C, Lozano M, Figueroa S, Espinoza A, Berger T, Mak TW, Jaisser F, Pacheco R, Michea L, Amador CA. Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation. J Hypertens. 2019 Feb 12. doi: 10.1097/HJH.0000000000002067.

Osorio-Barrios F, Prado C, Contreras F, Pacheco R. Dopamine Receptor D5 Signaling Plays a Dual Role in Experimental Autoimmune Encephalomyelitis Potentiating Th17-Mediated Immunity and Favoring Suppressive Activity of Regulatory T-Cells. Front Cell. Neurosci. 2018 Jul 10; 12:192.

Prado C, Iruretagoyena M, Burgos PI, Pacheco R. Smoking promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients. Rev Med Chil. 2018 Feb; 146(2):150-159.

Prado C, Gaiazzi M, González H, Ugalde V, Figueroa A, Osorio-Barrios FJ, López E, Lladser A, Rasini E, Marino F, Zaffaroni M, Cosentino M, Pacheco R. Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis. Front Immunol. 2018 Mar 21; 9:571

Hevia D, Araos P, Prado C, Fuentes Luppichini E, Rojas M, Alzamora R, Cifuentes-Araneda F, Gonzalez AA, Amador CA, Pacheco R, Michea L. Myeloid CD11c+ Antigen-Presenting Cells Ablation Prevents Hypertension in Response to Angiotensin II Plus High-Salt Diet. Hypertension. 2018 Apr; 71(4):709- 718.

Figueroa C, Gálvez-Cancino F, Oyarce C, Contreras F, Prado C, Valeria C, Cruz S, Lladser A, Pacheco. Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity. J Neuroimmunol. 2017 Feb 15; 303:99-107.

Doñas C, Carrasco M, Fritz M, Prado C, Tejón G, Osorio-Barrios F, Manríquez V, Pacheco R, Reyes P, Bono MR, Loyola A, Rosemblatt M. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs. J Autoimmun. 2016; 75:105-117.

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. 2016 May 15; 196(10):4143-9.

Oliva H, Pacheco R, Martinez-Navio JM, Rodríguez-García M, Naranjo-Gómez M, Climent N, Prado C, Gil C, Plana M, García F, Miró JM, Franco R, Borras FE, Navaratnam N, Gatell JM, 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. 2016 Aug;94(7):689-700.

Gómez R; Ramírez B; Cespedes P; Cautivo K; Riquelme S; Prado C; Gonzalez, P; Kalergis A. Contribution of Fcγ Receptors to Human Respiratory Syncytial Virus Pathogenesis and the Impairment of T cell Activation by Dendritic Cells. Immunol. 2016 Jan; 147(1):55-72

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. 2015 Jul 15;284:18-29

Prado C, Bernales S, Pacheco R. Modulation of T-cell mediated immunity by dopamine receptor D5. Endocr Metab Immune Disord Drug Targets. 2013 Jun; 13(2):184-94.

Gonzalez H, Contreras F, Prado CE, Elgueta D, Franz D, Bernales S, Pacheco R. Dopamine receptor D3 expressed on CD4+ T-cells favours neurodegeneration of dopaminergic neurons during Parkinson’s disease. J Immunol, 2013 May 15; 190(10):5048-56. 2012

Prado C, Contreras F, González H, Díaz P, Elgueta D, Barrientos M, Herrada AA, Lladser Á, Bernales S, Pacheco R. Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol. 2012 Apr 1; 188(7): 3062-70. 2009

Pacheco R, Prado CE, Barrientos MJ, Bernales S. Role of dopamine in the physiology of Tcells and  dendritic cells. J Neuroimmunol. 2009 Nov 30; 216(1-2):8-19.

González PA, Prado CE, Leiva ED, Carreño LJ, Bueno SM, Riedel CA, Kalergis AM. Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells. Proc Natl Acad Sci USA. 2008 Sep 30; 105(39):14999-5004.

Bueno SM, González PA, Pacheco R, Leiva ED, Cautivo KM, Tobar HE, Mora JE, Prado CE, Zúñiga JP, Jiménez J, Riedel CA, Kalergis AM. Host immunity during RSV pathogenesis. Int Immunopharmacol. 2008 Oct; 8(10):1320-9.

 

Principal investigator

Carolina Prado

+5623672052

cprado@cienciavida.org

Biography

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