Article

TSLP and immune homeostasis.

Department of Immunology, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, TX 77004, USA.
Allergology International 03/2012; 61(1):19-25. DOI: 10.2332/allergolint.11-RAI-0394
Source: PubMed

ABSTRACT In an immune system, dendritic cells (DCs) are professional antigen-presenting cells (APCs) as well as powerful sensors of danger signals. When DCs receive signals from infection and tissue stress, they immediately activate and instruct the initiation of appropriate immune responses to T cells. However, it has remained unclear how the tissue microenvironment in a steady state shapes the function of DCs. Recent many works on thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine that has the strong ability to activate DCs, provide evidence that TSLP mediates crosstalk between epithelial cells and DCs, involving in DC-mediated immune homeostasis. Here, we review recent progress made on how TSLP expressed within the thymus and peripheral lymphoid and non-lymphoid tissues regulates DC-mediated T-cell development in the thymus and T-cell homeostasis in the periphery.

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    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.
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