Modulation of experimental arthritis induced by the association of ovalbumin and type II collagen

Author(s)

Rodolfo Thomé

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2011-07-22

Examining board members

Wirla Maria da Silva Cunha Tamashiro; Alexandrina Sartori; Ronei Luciano Mamoni

• Advisor: Wirla Maria da Silva Cunha Tamashiro; Patricia Ucelli Simioni

Abstract

BALB/c mice, genetically resistant to collagen-induced arthritis (CIA), can develop a inflammatory condition resembling what is observed in susceptible strains when a non-related protein, such as ovalbumin (OVA), is associated with type II collagen (CII). Using this model, we evaluated whether oral tolerance to OVA could interfere in the immune response against CII, as well as the effect of adoptive transfer of tolerogenic dendritic cells (DCs) to arthritic mice. In order to evaluate the effect of oral tolerance over arthritis development in BALB/c mice, animals were fed with OVA in the drinking water at a 4mg/mL concentration, for seven consecutive days, before or after challenge with CII+OVA (100?g of each antigen). In order to evaluate the participation of tolerogenic DCs in the modulation of arthritis, splenic CD11c+ cells were isolated from OVA tolerant mice and adoptively transferred to naïve mice, which were subsequently immunized with CII+OVA. In order to monitor the evolution of the severity of arthritis, we evaluated paw edema, taking paw thickness regularly measured; performed histological analyses of articular knee tissues and, conducted ex-vivo evaluation of serum specific antibody levels and proliferation and cytokine secretion of splenic T lymphocytes. The treatment with OVA before CIA induction prevented the development of arthritis in all analyzed parameters, while the treatment after disease onset significantly reduced inflammation and CII-specific antibody production. We also observed that tolerogenic DC transfer prevented the appearance of clinical signs of arthritis, the increase of serum specific antibody levels and significantly reduced CII-specific T lymphocytes proliferation. While the frequency of CD4+CD25+Foxp3+ cells were higher in cell culture from tolerogenic DC recipient mice, frequency of IFN?- and IL-17- producing cells were significantly reduced. We observed that levels of TGF-?, IL-4 and IL-10 were significantly higher in cultures of splenic cells from mice recipient of tolerogenic DC, while levels of IFN-?, IL-6 and TNF-? were reduced. Taken together, our results indicate that oral tolerance to a non-related antigen modifies the course of experimental arthritis in response to collagen, and that dendritic cells with a tolerogenic profile are involved in the observed phenomena (AU)

• FAPESP's process: 09/01838-2 - Modulation of experimental arthritis induced by the association of ovalbumin and type II collagen
• Grantee: Rodolfo Thomé
• Support Opportunities: Scholarships in Brazil - Master