Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice

Author(s)

Paiatto, Lisiery N. ^[1] ; Silva, Fernanda G. D. ^{[2, 3]} ; Yamada, Aureo T. ^[4] ; Tamashiro, Wirla M. S. C. ^[5] ; Simioni, Patricia U. ^{[1, 5, 6]}

Affiliation

^[1] Univ Estadual Paulista, UNESP, Inst Biosci, Rio Claro, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Fac Food Engn, Campinas, SP - Brazil

^[3] Univ Fed Ouro Preto, Sch Nutr, Dept Food, Ouro Preto, MG - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[5] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas, SP - Brazil

^[6] Fac Amer, FAM, Dept Biomed Sci, Americana, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 13, n. 5 MAY 8 2018.
• Web of Science Citations: 0

Abstract

Introduction In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naive and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. Methods and results To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naive (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100 mu g2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11(+) MHC II+ and CD11(+) MHCII+ CD86(+) cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naive mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17(+)CD4(+) cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of that no competing interests exist. IL-9 and IFN-gamma were lower in supernatants of cells from mice treated with nDCs. Conclusion The results allow us to conclude that the adoptive transfer of cells expressing CD11c is able to reduce the clinical and immunological signs of drug-induced colitis. Adoptive transfer of CD11c(+)DC isolated from both naive and tolerant mice altered the proliferative and T cell responses. To the best of our knowledge, there is no previously published data showing the protective effects of DCs from naive or tolerant mice in the treatment of colitis. (AU)

• FAPESP's process: 13/20258-2 - Effects of oral tolerance and tolerogenic dendritic cell administration on the immune response in experimental colitis
• Grantee: Patricia Ucelli Simioni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/09326-1 - Immunohistological evaluation of colon cell populations after adoptive transfer of dendritic cells treated with indomelamine modulators in experimental colitis induced by TNBS
• Grantee: Caique Lopes Souza
• Support Opportunities: Scholarships in Brazil - Scientific Initiation