Dendritic Cell-Intrinsic Expression of NF-κB1 Is Required to Promote Optimal Th2 Cell Differentiation

Artis, David; Kane, Colleen; Fiore, James; Zaph, Colby; Shapira, Sagi; Joyce, Karen L.; MacDonald, Andrew S.; Hunter, Christopher A.; Scott, Phillip; Pearce, Edward J.

doi:10.4049/jimmunol.174.11.7154

Cited by 53 publications

(48 citation statements)

References 33 publications

(44 reference statements)

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“…In the T-cell lineage, nfkb1 is dispensable for thymocyte maturation (Sha et al, 1995), but is required to generate normal Th2 responses involving the effector cytokines interleukin (IL)-4, IL-5 and IL-13 (Das et al, 2001;Artis et al, 2005). This defect is due in part to a failure of nfkb1 À/À dendritic cells (DC) to promote Th2 differentiation (Artis et al, 2005).…”

Section: Nf-kb P50/p105mentioning

confidence: 99%

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Unravelling the complexities of the NF-κB signalling pathway using mouse knockout and transgenic models

et al. 2006

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The nuclear factor-jB (NF-jB) signalling pathway serves a crucial role in regulating the transcriptional responses of physiological processes that include cell division, cell survival, differentiation, immunity and inflammation. Here we outline studies using mouse models in which the core components of the NF-jB pathway, namely the IjB kinase subunits (IKKa, IKKb and NEMO), the IjB proteins (IjBa, IjBb, IjBe and Bcl-3) and the five NF-jB transcription factors (NF-jB1, NF-jB2, c-Rel, RelA and RelB), have been genetically manipulated using transgenic and knockout technology.

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Section: Nf-kb P50/p105mentioning

confidence: 99%

“…This defect is due in part to a failure of nfkb1 À/À dendritic cells (DC) to promote Th2 differentiation (Artis et al, 2005). A role for p50/p105 in the formation of Th1 cells remains unclear.…”

Section: Nf-kb P50/p105mentioning

confidence: 99%

Unravelling the complexities of the NF-κB signalling pathway using mouse knockout and transgenic models

et al. 2006

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“…We have shown previously that exposure of DC to Schistosoma mansoni-soluble egg Ag (SEA) conditions them to drive Th2 responses, a process that is dependent upon DC expression of MHC class II (MHC II) (24), NF-B (25), and CD40 (26). In this study, we have directly addressed the importance of DC expression of OX40L in Th2 induction by transferring OX40L-deficient Agloaded DC into OX40L ϩ/ϩ (WT) recipient mice.…”

Section: Cd4mentioning

confidence: 99%

Dendritic Cell Expression of OX40 Ligand Acts as a Costimulatory, Not Polarizing, Signal for Optimal Th2 Priming and Memory Induction In Vivo

Jenkins

Perona-Wright

Worsley

et al. 2007

The Journal of Immunology

121

115

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Costimulatory cross-talk can occur at multiple cellular levels to potentiate expansion and polarization of Th responses. Although OX40L ligand (OX40L) is thought to play a key role in Th2 development, the critical cellular source of this molecule has yet to be identified. In this study, we demonstrate that OX40L expression by the initiating dendritic cell (DC) is a fundamental requirement for optimal induction of primary and memory Th2 responses in vivo. Analysis of the kinetics of the residual Th2 response primed by OX40L-deficient DC suggested a failure to stimulate appropriate expansion and/or survival of T cells, rather than an inability to polarize per se. The dependence upon OX40L was predominantly due to the provision of signaling through OX40 rather than retrograde signaling to the DC. Mechanistically, impaired Th2 priming in the absence of OX40L was not due to exaggerated regulation because there was no evidence of increased expansion or function of regulatory cell populations, suppression through IL-10 production, or hyporesponsiveness to secondary challenge. These data define a critical role for DC-derived OX40L in the induction and development of Th2 responses in vivo.

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“…As a result, ERK has been implicated in conditioning DC for Th2 priming [11,30,31]. Likewise, signaling through NF-kB1 appears to be important for priming of DC for Th2 polarization, since both SEA- [32] and LNFPIII-pulsed NF-kB1-deficient DC [29] are incapable of inducing a Th2 response (Fig. 1).…”

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

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The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

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Dendritic Cell-Intrinsic Expression of NF-κB1 Is Required to Promote Optimal Th2 Cell Differentiation

Cited by 53 publications

References 33 publications

Unravelling the complexities of the NF-κB signalling pathway using mouse knockout and transgenic models

Unravelling the complexities of the NF-κB signalling pathway using mouse knockout and transgenic models

Dendritic Cell Expression of OX40 Ligand Acts as a Costimulatory, Not Polarizing, Signal for Optimal Th2 Priming and Memory Induction In Vivo

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

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