TRAF6 Is a Critical Factor for Dendritic Cell Maturation and Development

Kobayashi, Takashi; Walsh, Patrick; Walsh, Matthew C.; Speirs, Kendra; Chiffoleau, Elise; King, Catrina E.; Hancock, Wayne W.; Caamaño, Jorge; Hunter, Christopher A.; Scott, Phillip; Turka, Laurence A.; Choi, Yongwon

doi:10.1016/s1074-7613(03)00230-9

Cited by 248 publications

(223 citation statements)

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“…Defective osteoclastogenesis observed in nik −/− mice can be restored by overexpressing RelB, but not RelA, indicating a specific function of RelB in osteoclast differentiation [84]. Further, specific expression of relb transcripts was found in antigen-presenting cells, and requirement of RelB for CD4 + CD8α − dendritic cell development was reported [85][86][87]. Even though the physiological function of RelB in DC and MZB cell development has been established, the mechanistic aspects of its regulation and the downstream target gene expression programs have not been revealed.…”

Section: The Non-canonical Pathwaymentioning

confidence: 99%

A single NFκB system for both canonical and non-canonical signaling

et al. 2010

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Two distinct nuclear factor κB (NFκB) signaling pathways have been described; the canonical pathway that mediates inflammatory responses, and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis. The former is dependent on the IκB kinase adaptor molecule NEMO, the latter is independent of it. Here, we review the molecular mechanisms of regulation in each signaling axis and attempt to relate the apparent regulatory logic to the physiological function. Further, we review the recent evidence for extensive cross-regulation between these two signaling axes and summarize them in a wiring diagram. These observations suggest that NEMO-dependent and -independent signaling should be viewed within the context of a single NFκB signaling system, which mediates signaling from both inflammatory and organogenic stimuli in an integrated manner. As in other regulatory biological systems, a systems approach including mathematical models that include quantitative and kinetic information will be necessary to characterize the network properties that mediate physiological function, and that may break down to cause or contribute to pathology.

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Section: The Non-canonical Pathwaymentioning

confidence: 99%

A single NFκB system for both canonical and non-canonical signaling

et al. 2010

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“…Other genes, i.e. Krüppel family of zinc finger transcription factor Ikaros C, transcription factor PU.1, IRF-2 and IRF-4 (IFN regulatory factor-2 and -4), Notch-dependent transcription factor RBP-J, and TRAF6 (TNF receptor associated factor-6), have also been described to play a role in differentiation of CD4+ DC subset [36][37][38][39][40][41]. The Ig superfamily member, CD40 and Toll-like receptors are receptors known to signal through TRAF6, yet none of those TNFR are implicated in the regulation of DC homeostasis.…”

Section: Noncanonical Nfκb Signaling Cascade Regulates DC Homeostasismentioning

confidence: 99%

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Trez

Ware

2008

Cytokine & Growth Factor Reviews

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Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets.Keywords dendritic cells; homeostasis; TNF superfamily; cosignaling; lymphotoxin; herpesvirus entry mediator Dendritic CellsDendritic cells (DC) originate from hematopoietic precursors and can be divided in several subsets depending on their anatomical location, surface phenotype and function. For example, two broad classes of DC are the peripheral migratory DC and the lymphoid tissue-resident DC [1]. The migratory DC, i.e. the dermal DC and Langerhans cells, can be considered as sentinels of the immune system as they form a sensing barrier in peripheral tissues at the interface with environment. The lymphoid tissue-resident DC include the splenic and thymic DC.Dendritic cells are specialized in the capture, transport, processing and presentation of antigens. In the presence of a microbial stimulus, these steps are associated with further DC differentiation (maturation) characterized by upregulation of costimulatory and major histocompatibility complex (MHC) molecules. As DC become activated they migrate to or Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Both spleen and lymph node lymphoid tissue-resident DC possess a half-life of about three days. Despite their rapid turnover, little is known about the factors controlling immediate precursors and homeostasis in vivo. In earlier studies, CD8α expression was used to distinguish between "lymphoid" and "myeloid" DC. However, more recent experiments showed that different DC subsets could differentiate from both lymphoid and myeloid precursors [6,7]. CD8α marker remains very useful to discriminate between subsets, but no longer defines a subset origin. Recently, the group of Shortman provided in vivo and in vitro evidence fo...

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“…TRAF6 was firstly identified by Ishida's (Ishida et al, 1996) and it binds to the amino-terminal region of the CD40 cytoplasmic tail, which is distinct from the binding domain for TRAF2, TRAF3, and TRAF5. Meanwhile, TRAF6 plays a critical role in immune (Kobayashi et al, 2003) and inflammation. Unlike other TRAFs, it is also involved in IL-1 signaling, leading to the activation of NF-kB (nuclear factor kappaB) (Ishida et al, 1996;Lee and Lee, 2002).…”

Section: Introductionmentioning

confidence: 99%