TSLP production by dendritic cells is modulated by IL‐1β and components of the endoplasmic reticulum stress response

Elder, Matthew J.; Webster, Steve J.; Williams, David L.; Gaston, Hill; Goodall, Jane C.

doi:10.1002/eji.201545537

Cited by 44 publications

(49 citation statements)

References 46 publications

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“…Previous work has highlighted the importance of IL-1β secretion in orchestrating dectin-1-mediated immune responses (12, 16, 23). Therefore, we examined whether the amount of IL-1β stimulated by β-glucan particles of different sizes is critical in determining the amounts of other cytokines produced.…”

Section: Resultsmentioning

confidence: 99%

β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

et al. 2017

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Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs) required for antifungal immunity. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to β-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1β production determined by β-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that β-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.

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Section: Resultsmentioning

confidence: 99%

β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

et al. 2017

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“…Initially, TSLP was shown to prime DCs for adaptive Th2 responses and this role was thought to be primarily responsible for downstream type 2 inflammation driven by TSLP [ 26 ]. In addition to responding to TSLP, a recent human study showed that dendritic cells exposed to fungal allergen are also a potent source of TSLP [ 31 ]. Furthermore, recent studies have identified basophils and mast cells as additional sources of TSLP [ 32 ].…”

Section: Thymic Stromal Lymphopoietin (Tslp)mentioning

confidence: 99%

Cytokine and Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells(ILC2s) in Human Allergic Airway Disease

Cavagnero¹,

Doherty²

2017

J Cytokine Biol

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The recent discovery of group 2 innate lymphoid cells (ILC2s) has caused a paradigm shift in the understanding of allergic airway disease pathogenesis. Prior to the discovery of ILC2s, Th2 cells were largely thought to be the primary source of type 2 cytokines; however, activated ILC2s have since been shown to contribute significantly, and in some cases, dominantly to type 2 cytokine production. Since the discovery of ILC2s in 2010, many mediators have been shown to regulate their effector functions. Initial studies identified the epithelial derived cytokines IL-25, IL-33, and TSLP as activators of ILC2s, and recent studies have identified many additional cytokine and lipid mediators that are involved in ILC2 regulation. ILC2s and their mediators represent novel therapeutic targets for allergic airway diseases and intensive investigation is underway to better understand ILC2 biology and upstream and downstream pathways that lead to ILC2-driven airway pathology. In this review, we will focus on the cytokine and lipid mediators that regulate ILC2s in human allergic airway disease, as well as highlight newly discovered mediators of mouse ILC2s that may eventually translate to humans.

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“…In mice, intratumoral application of Curdlan was found to reprogram infiltrating DCs to become resistant to cancer‐derived thymic stromal lymphopoietin (TSLP), thus favoring the generation of beneficial Th1‐based immune responses . In contrast, during microbial infections, Dectin‐1 activation induced TSLP release by DCs, thus promoting Th2‐biased immunity . However, the importance of DC‐intrinsic TSLP production in the context of tumor immunity remains to be determined.…”

Section: Resultsmentioning

confidence: 99%

Card9 controls Dectin‐1‐induced T‐cell cytotoxicity and tumor growth in mice

et al. 2017

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Activation of the C‐type lectin receptor Dectin‐1 by β‐glucans triggers multiple signals within DCs that result in activation of innate immunity. While these mechanisms can potently prime CD8+ cytotoxic T‐cell (CTL) responses without additional adjuvants, the Dectin‐1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin‐1‐induced CTL cross‐priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro. In vivo, Dectin‐1‐mediated Card9 activation after vaccination drives both expansion and activation of Ag‐specific CTLs, resulting in long‐lasting CTL responses that are sufficient to protect mice from tumor challenge. This Dectin‐1‐induced antitumor immune response was independent of NK cell function and completely abrogated in Card9‐deficient mice. Thus, our results demonstrate that Dectin‐1‐triggered Card9 signaling but not inflammasome activation can potently cross‐prime Ag‐specific CTLs, suggesting that this pathway would be a candidate for immunotherapy and vaccine development.

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TSLP production by dendritic cells is modulated by IL‐1β and components of the endoplasmic reticulum stress response

Cited by 44 publications

References 46 publications

β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

Cytokine and Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells(ILC2s) in Human Allergic Airway Disease

Card9 controls Dectin‐1‐induced T‐cell cytotoxicity and tumor growth in mice

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