Effects of oral tolerance and tolerogenic dendritic cell administration on the immune response in experimental colitis

Abstract

Although the etiology of most autoimmune diseases is not known, the breakdown of immune tolerance to self-antigens is a generating mechanism common to these deleterious immune responses. Various strategies have been proposed to modulate the autoimmune responses, among which stand out the adoptive transfer of tolerogenic cells and/or treatment with regulatory cytokines. Moreover, several studies have shown that the ingestion of dietary protein antigens can generate indirect effects on the host immune system, characterized by suppressing immune response to antigenically unrelated proteins known as bystander suppression. Based on this assumption, we analyze the indirect effects of oral tolerance induced by the ingestion of ovalbumin (OVA) in TNBS -induced colitis, as well as the effects of adoptive transfer of tolerogenic dendritic cells to these animals. Still in the context of tolerance, current studies have indicated an important role of CTLA-4 molecule in the expression of indoleamine 2, 3-dioxygenase (IDO), an enzyme produced by dendritic cells, which acts on tryptophan and appears to exert a regulatory effect on the immune response. For this reason, we also evaluate the effects of the adoptive transfer of bone marrow derived dendritic cells (BMDCs) treated with CTLA-4-Ig or with IDO modulator. After treatment, the following parameters will be assessed: change in body weight; histology of target tissues; cell proliferation; cytokine production and expansion of CD25+ Foxp3+ regulatory T cells and TH17 cells in cultures of splenocytes. Our hypothesis is that the context generated by the immune response to antigens of the diet as well as modulation of IDO can reduce the damage observed in autoimmune diseases, both systemic and organ-specific. The mechanisms involved in reduction of damage may be related to the action of Treg cells, secretion of suppressive cytokines, and expression of IDO and costimulatory molecules. (AU)