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 (Impact Factor: 2.46). 03/2012; 61(1):19-25. DOI: 10.2332/allergolint.11-RAI-0394
Source: PubMed


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.

Download full-text


Available from: · License: CC BY-NC-ND
  • Source
    • "Thus far, it is unclear how DCs respond to combined simultaneous stimulation by TSLP and TLR ligands. This question was addressed for mDCs showing synergy between TSLP and TLR ligands in Th polarization [16–18]. No studies to date have investigated combined TSLP-TLR ligand engagement of pDCs. "
    [Show abstract] [Hide abstract]
    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/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-α 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.
    Full-text · Article · Dec 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thymic stromal lymphopoietin (TSLP), highly expressed in keratinocytes in atopic dermatitis patients and bronchial epithelial cells in asthma patients, plays a key role in allergic diseases. Two forms of TSLP mRNA (long and short) have been reported. We compared the expression of the long-form and total TSLP transcripts in primary human keratinocytes. Primary human keratinocytes were stimulated with Toll-like receptor (TLR) ligands, cytokines, and vitamin D receptor agonists. Gene expression was analyzed by quantitative real-time PCR. The amount of TSLP released was measured by ELISA. PolyI:C (TLR3 ligand), FSL-1 (TLR2-TLR6 ligand) and flagellin (TLR5 ligand) upregulated long-form TSLP expression, which predominantly contributed to upregulation of total TSLP expression. A glucocorticoid or an endosomal acidification inhibitor inhibited the polyI:C-dependent upregulation of total TSLP and the decrease of the total TSLP was due to the decrease of the long-form. An atopic cytokine milieu (TNF-α+IL-4+IL-13) or TNF-α alone also upregulated the long-form. These stimuli also induced the release of TSLP. In contrast, a high concentration of calcitriol (1,25-dihydroxyvitamin D(3), the active form of vitamin D(3)) or its analog MC903 upregulated total TSLP significantly but not the long-form, and did not induce the release of TSLP. TLR ligands or cytokines predominantly upregulate the gene expression of the long TSLP form, which contributes to the TSLP protein production, in primary human keratinocytes. Specific measurement of the long-form rather than total TSLP should be useful for accurate detection of functional human TSLP gene expression.
    No preview · Article · Mar 2012 · Journal of dermatological science
  • [Show abstract] [Hide abstract]
    ABSTRACT: The substantial increase in the worldwide prevalence of asthma and atopy has been attributed to lifestyle changes that reduce exposure to bacteria. A recent insight is that the largely bacterial microbiome maintains a state of basal immune homoeostasis, which modulates immune responses to microbial pathogens. However, some respiratory viral infections cause bronchiolitis of infancy and childhood wheeze, and can exacerbate established asthma; whereas allergens can partly mimic infectious agents. New insights into the host's innate sensing systems, combined with recently developed methods that characterise commensal and pathogenic microbial exposure, now allow a unified theory for how microbes cause mucosal inflammation in asthma. The respiratory mucosa provides a key microbial interface where epithelial and dendritic cells interact with a range of functionally distinct lymphocytes. Lymphoid cells then control a range of pathways, both innate and specific, which organise the host mucosal immune response. Fundamental to innate immune responses to microbes are the interactions between pathogen-associated molecular patterns and pattern recognition receptors, which are associated with production of type I interferons, proinflammatory cytokines, and the T-helper-2 cell pathway in predisposed people. These coordinated, dynamic immune responses underlie the differing asthma phenotypes, which we delineate in terms of Seven Ages of Asthma. An understanding of the role of microbes in the atopic march towards asthma, and in causing exacerbations of established asthma, provides the rationale for new specific treatments that can be assessed in clinical trials. On the basis of these new ideas, specific host biomarkers might then allow personalised treatment to become a reality for patients with asthma.
    No preview · Article · Feb 2013 · The Lancet
Show more

Similar Publications