Plasmacytoid DCs, exposed to TSLP in synergy with TLR ligands, acquire significant potential towards Th2 polarization
Abstract
BACKGROUND: Thymic stromal lymphopoietin (TSLP) has been reported to activate myeloid dendritic cells (mDCs) to induce Th2 T lymphocyte responses. Its effect on plasmacytoid dendritic cells (pDCs) with TLR ligands has not yet been studied.
We investigated the effects of TSLP and TLR ligands on mDCs and pDCs subsets. MATERIAL AND METHODS: Myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were stimulated by TLR ligands (mDC with TLR1/2 LTA, TLR2 PGN, TLR3 poly I: C, TLR4 LPS, TLR5 Flagellin) (pDC with TLR9 CpG2006, CpG 2216, TLR7 loxoribine) in the presence or absence of TSLP.
Supernatants from mDCs and pDCs were analyzed for cytokine production. mDCs and pDCs were collected and cultured with allogeneic naïve T cells and after 7 days of co-culture. DC-primed CD4+ T cells were washed and restimulated with PMA and ionomycin.
Cytokine production in supernatants from restimulated cells - IL-4, IL-5, IL-10, IL-13, TNF-a was analyzed by Luminex. RESULTS: TSLP alone induced the expression of maturation markers on mDCs and increased their ability to polarize lymphocytes into the Th2 phenotype.
We demonstrated that pDCs also have the capacity to become even more potent inducers of Th2 immune responses, but only after combined treatment with TSLP and TLR ligands, particularly with TLR9 ligand CpG 2006. CONCLUSIONS: TSLP plays a major role in Th2 polarization of immune response mediated by myeloid DCs.
Here, we demonstrate that plasmacytoid DCs, exposed to TSLP together with TLR ligands, acquire significant potential towards Th2 polarization.