PMID- 35202987 OWN - NLM STAT- MEDLINE DCOM- 20220506 LR - 20220506 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 152 DP - 2022 Apr TI - Aqueous extract of Passiflora alata leaves modulates in vitro the indoleamine 2,3-dioxygenase (IDO) and CD86 expression in bone marrow-derived professional antigen-presenting cells polarizing NOD mice T cells to a Treg profile. PG - 155832 LID - S1043-4666(22)00041-2 [pii] LID - 10.1016/j.cyto.2022.155832 [doi] AB - Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (pAPCs), numerous in the pancreas of nonobese diabetic (NOD) mice and playing an essential role in the autoimmune response of type 1 diabetes. The expression of the enzyme indoleamine 2,3-dioxygenase (IDO) is a critical factor for the tolerogenic activity of pAPCs, acting in the catabolism of tryptophan, providing metabolites that suppress the T cell effectors and induce T regulatory cells differentiation. Here we investigated the in vitro mechanisms of lyophilized aqueous extract from Passiflora alata leaves (LAEPAL) that modulates bone marrow-derived professional antigen-presenting cells (BM-pAPCs), affecting their ability to polarize T cells. A cell culture model was defined using mixed cultures of BM-pAPCs and T lymphocytes NOD mice with stressed MIN-6 cells as a source of pancreatic beta cells antigens. We showed that the treatment with 300 microg/mL of LAEPAL induces a significant decrease in the CD4 and CD8 T effector lymphocytes proliferation from diabetic but not in non-diabetic mice, followed by a reduction of the IL-6 and IFN-gamma cytokines release in the cell cultures supernatants. Moreover, we observed an increase of CD4(+)CD25(+)FoxP3(+) Tregs in the cell cultures from diabetic mice. These results could be partially explained by the LAEPAL modulatory effects in BM-pAPCs, downregulating the CD86 co-stimulatory molecule expression, and increasing IDO-1 expression in F4/80+ BM-pAPCs. These results contribute to a better understanding of the polyphenols' immunomodulatory properties, meaning they could induce tolerogenic antigen-presenting cells, which could polarize T cells to a Treg profile and decrease the activity of CD4+ and CD8+ T effector cells. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Schumacher, Nayara Simon Gonzalez AU - Schumacher NSG AD - Laboratory of Translational Immunology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil. Electronic address: n144325@dac.unicamp.br. FAU - Fernandes, Luis Gustavo Romani AU - Fernandes LGR AD - Laboratory of Translational Immunology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil. Electronic address: luisgrf@unicamp.br. FAU - de Lima Zollner, Ricardo AU - de Lima Zollner R AD - Laboratory of Translational Immunology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil. Electronic address: zollner@unicamp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220221 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antigens) RN - 0 (B7-2 Antigen) RN - 0 (Cd86 protein, mouse) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) SB - IM MH - Animals MH - Antigen-Presenting Cells/metabolism MH - Antigens MH - B7-2 Antigen/metabolism MH - Bone Marrow/metabolism MH - Cells, Cultured MH - Dendritic Cells MH - *Diabetes Mellitus, Experimental MH - Humans MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism MH - Mice MH - Mice, Inbred NOD MH - *Passiflora/metabolism MH - Plant Leaves MH - T-Lymphocytes, Regulatory OTO - NOTNLM OT - Antigen-presenting cells and Passiflora alata OT - NOD mice OT - Type 1 diabetes mellitus EDAT- 2022/02/25 06:00 MHDA- 2022/05/07 06:00 CRDT- 2022/02/24 20:14 PHST- 2021/03/25 00:00 [received] PHST- 2022/02/03 00:00 [revised] PHST- 2022/02/15 00:00 [accepted] PHST- 2022/02/25 06:00 [pubmed] PHST- 2022/05/07 06:00 [medline] PHST- 2022/02/24 20:14 [entrez] AID - S1043-4666(22)00041-2 [pii] AID - 10.1016/j.cyto.2022.155832 [doi] PST - ppublish SO - Cytokine. 2022 Apr;152:155832. doi: 10.1016/j.cyto.2022.155832. Epub 2022 Feb 21.