Regulation of JAK/STAT/SOCS in the ontogen of IFNg-producing cells derivated from encephalitogenic Th17 cells during the clinical evolution of experimental autoimmune encephalomyelitis

• Grant number: 17/21363-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2018
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alessandro dos Santos Farias
• Grantee: Alessandro dos Santos Farias
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative autoimmune disease of the central nervous system (CNS), in which encephalitogenic lymphocytes attack and destroy myelin, interfering with the transmission of electrical signal and therefore, in the communication between neurons. In the Experimental autoimmune encephalomyelitis (EAE), experimental model of MS, it has been shown that two subtypes of lymphocytes (Th1 and Th17) act in a synergistic and coordinated manner during the development of the disease. Particularly during clinical stage of the disease, clones "Th17" begin to express IFNg after entering the CNS, assuming a "Th1" profile. Thus, it is possible for the same encephalitogenic clones to assume distinct profiles during the progression of the disease. The resulting microenvironment of cytokines released seems to be the main factor to influence the differentiation and function of T lymphocytes. Cytokines transmit its signal by binding to receptors of cytokine associated with Janus kinases (JAKs), culminating in the phosphorylation of signal transducers and activators of transcription (STATs). STATs induce transcription of suppressor of signals of cytokines (SOCS), SOCS proteins control cytokines responses. Therefore, it is possible that these CD4+ T encephalitogenic lymphocytes that change their expression of cytokines have a regulation of the JAK/STAT/SOCS pathway which have not been described in the literature yet. The aim of this study is to evaluate the regulation of this pathway in CD4+ encephalitogenic lymphocytes during the clinical development of EAE; more specifically, how is the control of the profile change of "Th17" for "Th1"(or producers of IFNg) after these cells enter the CNS. STATs fosforilation will be measured through PhosFlow cytometry in the different lymphocytes subtypes T CD4+ (IFNg+IL-17-, IFNg+IL-17+ e IFNg-IL-17+). These subtypes will be sorted to perform qPCR and analysis of SOCS family molecules expression. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S.. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, AUG 2020. (13/08216-2, 18/21934-5, 17/50137-3, 17/26170-0, 12/19278-6, 17/22504-1, 17/21363-5, 18/14933-2, 19/06372-3)

BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S.. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, v. 108, n. 4, p. 9-pg., 2020-08-10. (17/22504-1, 13/08216-2, 18/14933-2, 19/06372-3, 17/21363-5, 17/26170-0, 12/19278-6, 17/50137-3, 18/21934-5)

BOLDRINI, VINICIUS O.; BRANDAO, CARLOS OTAVIO; PIMENTEL, V, MARIA LUCIA; VIDAL, ALINE; MANSUR, LETICIA F.; QUINTILIANO, RAPHAEL P. S.; SANTOS, LEONILDA M. B.; FARIAS, ALESSANDRO S.. Massive activity of cytotoxic cells during refractory Neuromyelitis Optica spectrum disorder. Journal of Neuroimmunology, v. 340, MAR 15 2020. (17/21363-5, 15/22052-8, 12/01408-0, 19/06372-3)

PERON, J. P. S.; NAKAYA, H., I; SCHLINDWEIN, M. A. M.; GONCALVES, M. V. M.. COVID-19 Pandemic and Dysbiosis: Can the Ivermectin Hysteria Lead to an Increase of Autoimmune Neuroinflammatory Diseases?. CRITICAL REVIEWS IN IMMUNOLOGY, v. 40, n. 6, p. 6-pg., 2020-01-01. (17/22504-1, 19/06372-3, 13/08216-2, 17/21363-5, 18/14933-2, 18/21934-5, 12/19278-6)

PERON, J. P. S.; NAKAYA, I, H.; SCHLINDWEIN, M. A. M.; GONCALVES, M. V. M.. COVID-19 Pandemic and Dysbiosis: Can the Ivermectin Hysteria Lead to an Increase of Autoimmune Neuroinflammatory Diseases?. CRITICAL REVIEWS IN IMMUNOLOGY, v. 40, n. 6, SI, p. 537-542, 2020. (17/22504-1, 18/14933-2, 12/19278-6, 13/08216-2, 18/21934-5, 19/06372-3, 17/21363-5)

BOLDRINI, VINICIUS O.; QUINTILIANO, RAPHAEL P. S.; SILVA, LUCAS S.; DAMASCENO, ALFREDO; SANTOS, LEONILDA M. B.; FARIAS, ALESSANDRO S.. Cytotoxic profile of CD3+CD20+T cells in progressive multiple sclerosis. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 52, JUL 2021. (17/21363-5, 19/06372-3, 14/26431-0)

BOLDRINI, VINICIUS O.; MARQUES, ANA M.; QUINTILIANO, RAPHAEL P. S.; MORAES, ADRIEL S.; STELLA, CARLA R. A. V.; LONGHINI, ANA LEDA F.; SANTOS, IRENE; ANDRADE, MARILIA; FERRARI, BRENO; DAMASCENO, ALFREDO; et al. ytotoxic B Cells in Relapsing-Remitting Multiple Sclerosis Patient. FRONTIERS IN IMMUNOLOGY, v. 13, FEB 7 2022. (19/16116-4, 17/21363-5, 14/26431-0, 15/22052-8, 19/06372-3)

BOLDRINI, VINICIUS DE OLIVEIRA; FARIAS, ALESSANDRO DOS SANTOS; DEGASPERI, GIOVANNA ROSA. Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors. Scandinavian Journal of Immunology, v. 90, n. 4, JULY 2019. (17/21363-5)

BOLDRINI, VINICIUS OLIVEIRA; BRITO, MARIANA RABELO; QUINTILIANO, RAPHAEL PATRICIO SILVA; SCARDUA SILVA, LUCAS; YASUDA, CLARISSA LIN; CENDES, FERNANDO; FARIAS, ALESSANDRO SANTOS; DAMASCENO, ALFREDO. Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome. FRONTIERS IN NEUROLOGY, v. 14, p. 6-pg., 2023-08-17. (17/21363-5, 13/07559-3)