Immunomodulatory strategies in experimental arthritis based on induction of specific tolerance by vitamin D3 and rapamycin

• Grant number: 11/17325-4
• Support type: Regular Research Grants
• Duration: May 01, 2012 - October 31, 2014
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Alexandrina Sartori
• Grantee: Alexandrina Sartori
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Assoc. researchers: Gustavo Pompermaier Garlet

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which affects the joints. Most of current therapies for treating RA and other autoimmune diseases is based on the suppression of immune response in general, which increases susceptibility to infectious agents. The aim of this study is to define an immunomodulatory strategy for prophylaxis and/or therapy of RA. For this purpose, we will use a BALB/c experimental model of arthritis induced by immunization with proteoglycan (PG). Initially, two protocols for specific tolerance induction will be tested. Mice will be immunized with the specific antigen (PG) in the presence of vitamin D3 or rapamycin, and then submitted to an evaluation of its tolerogenic efficacy. The most tolerogenic protocol will then be used to test prophylactic and therapeutic potential and also the immunological mechanism underlying this effect. The humoral (specific antibody production), cellular (lymph nodes and spleen) and local immune responses (joints) will be evaluated. The humoral immune response will be checked by detection of serum anti-PG antibodies. The cellular immune response will be adressed by cytokine production (IL-1, IL-4, IL-6, TNF-alpha, IFN-gamma, IL-10 and IL-17) in spleen and lymph nodes cell cultures (ELISA) and by the characterization of Treg and dendritic cells (flow cytometry) in these organs. The local immune response (cytokine production and characterization of Th1, Th2 Th17 and Treg cells) will be determined by real time PCR from RNA obtained from joints. (AU)

Scientific publications

(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)

WATANABE ISHIKAWA, LARISSA LUMI; COLAVITE, PRISCILA MARIA; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; NISHIYAMA MIMURA, LUIZA AYUMI; DONEGA FRANCA, THAIS GRAZIELA; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; CHIUSO-MINICUCCI, FERNANDA; MARCOLINO, LARISSA DODDI; PENITENTI, MARCIMARA; VALERIO IKOMA, MAURA ROSANE; SARTORI, ALEXANDRINA. Vitamin D Deficiency and Rheumatoid Arthritis. CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, v. 52, n. 3, p. 373-388, JUN 2017. Web of Science Citations: 17.

WATANABE ISHIKAWA, LARISSA LUMI; COLAVITE, PRISCILA MARIA; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; NISHIYAMA MIMURA, LUIZA AYUMI; DONEGA FRANCA, THAIS GRAZIELA; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; CHIUSO-MINICUCCI, FERNANDA; DODDI MARCOLINO, LARISSA; MARQUES, CAMILA; VALERIO IKOMA, MAURA ROSANE; SARTORI, ALEXANDRINA. Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis. JOURNAL OF IMMUNOLOGY RESEARCH, 2016. Web of Science Citations: 0.

WATANABE ISHIKAWA, LARISSA LUMI; COLAVITE, PRISCILA MARIA; DA ROSA, LARISSA CAMARGO; BALBINO, BIANCA; DONEGA FRANCA, THAIS GRAZIELA; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; CHIUSO-MINICUCCI, FERNANDA; SARTORI, ALEXANDRINA. Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model. BIOMED RESEARCH INTERNATIONAL, 2014. Web of Science Citations: 5.