Protective effect of TSLP delivered at the gut mucosa level by recombinant lactic acid bacteria in DSS-induced colitis mouse model. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Aubry, Camille; Michon, Christophe; Chain, Florian; Chvatchenko, Yolande; Goffin, Laurence; Zimmerli, Simone; Leguin, Sylvia; Langella, Philippe; Bermudez-Humaran, Luis; Chatel, Jean-Marc
• Is Part Of: Microbial cell factories. Volume 14:Issue 1(2015)
• Page Start: 1
• Page End: 10
• Publication Date: 2015-12
• Subjects: TSLP -- Mucosal delivery -- Inflammatory bowel disease -- Lactococcus lactis; Microbial biotechnology -- Periodicals; Recombinant proteins -- Synthesis -- Periodicals; 660.62
• DOI: 10.1186/s12934-015-0367-5
• Languages: English
• ISSNs: 1475-2859

Abstract

Abstract Background Thymic stromal lymphopoietin (TSLP) is a cytokine known to mature dendritics cells, lower pro-inflammatory IL-12 secretion, induce differentiation of anti-inflammatory FoxP3+ regulatory T cells (Treg). Moreover, Crohn's disease patients have shown a reduction of intestinal TSLP expression. To understand the role of TSLP in inflammation, we constructedLactococcus lactis strain producing TSLP (LL-TSLP) and investigated the effect of its administration on dextran sulfate sodium (DSS)-induced colitis model in mice. Results LL-TSLP secrete an active molecule which lowers secretion of IL-12 by dendritic cells. Treatment with LL-TSLP, increases the amount of TGF-β secreted by T cells in Mesenteric Lymph Node in healthy mice. In acute DSS-induced colitis, LL-TSLP delayed the Disease Activity Index and lowered histological score and colonic INF-γ production. In a DSS-recovery model, LL-TSLP induced a better protective effect if the strain was administered at the beginning of the colitis. At Day 4 of colitis we observed an induction of Treg by LL-TSLP. Conclusions TSLP showed an anti-inflammatory protective role in DSS-induced colitis. We have demonstrated that a short and early administration of LL-TSLP is more efficient than a long lasting treatment.