Defective development of splenic and epidermal CD4<sup>+</sup>dendritic cells in mice deficient for IFN regulatory factor-2

Ichikawa, Eri; Hida, Shigeaki; Omatsu, Yoshiki; Shimoyama, Susumu; Takahara, Kazuhiko; Miyagawa, Shinichi; Inaba, Kayo; Taki, Shinsuke

doi:10.1073/pnas.0400610101

Cited by 116 publications

(97 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this report, previous studies have shown that RelB, like IRF-4, is expressed in myeloid DC, and is required for the development of CD4 + DC [2,15,16]. In addition to the above IRFs, IRF-2 is reported to be required for the development of CD4 + DCs [17,18]. Interestingly, IRF-2 acts by inhibiting IFNa/β suppression of DC development.…”

Section: Subset Development Specified By Irf-8 and Irf-4supporting

confidence: 76%

IRF family proteins and type I interferon induction in dendritic cells

2006

View full text Add to dashboard Cite

Dendritic cells (DC), although a minor population in hematopoietic cells, produce type I interferons (IFN) and other cytokines and are essential for innate immunity. They are also potent antigen presenters and regulate adaptive immunity. Among DC subtypes plasmacytoid DC (pDC) produce the highest amounts of type I IFN. In addition, pro-and anti-inflammatory cytokines such as IL-12 and IL-10 are induced in DC in response to Toll like receptor (TLR) signaling and upon viral infection. Proteins in the IRF family control many aspects of DC activity. IRF-8 and IRF-4 are essential for DC development. They differentially control the development of four DC subsets. IRF-8 -/-mice are largely devoid of pDC and CD8a+ DC, while IRF-4 -/-mice lack CD4 + DC. IRF-8, double knock-out mice have only few CD8á -CD4-DC that lack MHC II. IRF proteins also control type I IFN induction in DC. IRF-7, activated upon TLR signaling is required for IFN induction not only in pDC, but also in conventional DC (cDC) and non-DC cell types. IRF-3, although contributes to IFN induction in fibroblasts, is dispensable in IFN induction in DC. Our recent evidence reveals that type I IFN induction in DC is critically dependent on IRF-8, which acts in the feedback phase of IFN gene induction in DC. Type I IFN induction in pDC is mediated by MyD88 dependent signaling pathway, and differs from pathways employed in other cells, which mostly rely on TLR3 and RIG-I family proteins. Other pro-inflammatory cytokines are produced in an IRF-5 dependent manner. However, IRF-5 is not required for IFN induction, suggesting the presence of separate mechanisms for induction of type I IFN and other pro-inflammatory cytokines. IFN and other cytokines produced by activated DC in turn advance DC maturation and change the phenotype and function of DC. These processes are also likely to be governed by IRF family proteins. These cells express different sets of genes and assume distinct functions [2]. pDC produce the highest amounts of type I IFN, whereas DC8a + DC are a major producer of IL-12p40. Other DC subsets take part in producing other pro-inflammatory as well as anti-inflammatory cytokines including IL-10 and efficiently present antigens to T cells. Despite much progress have been made on studying DC biology, the origin and pathways that direct DC development are still unclear, and it appears that DC can be generated from different cell types through multiple pathways: for example, both common lymphoid precursors and common myeloid precursors are shown to be capable of generating similar DC subsets [3]. IRF-8 and IRF-4 share a number of common features. They are expressed only in the cells of the immune system. They both interact with PU.1, an immune cell specific protein of the Ets family and regulate genes

show abstract

Section: Subset Development Specified By Irf-8 and Irf-4supporting

confidence: 76%

IRF family proteins and type I interferon induction in dendritic cells

2006

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

“…Transcription factors of the IFN regulatory factor (IRF) family play crucial roles in differentiation as well as in the functional activity of DCs. GM-CSF-dependent development of DCs depends on IRF4 (46), as well as IRF2 (47,48). In addition, RelB, a member of the NF-B family, is required for the development of some subsets of DCs (49,50).…”

Section: Tsa Blocks Gm-csf-dependent Differentiation To Dcsmentioning

confidence: 99%

Deacetylase Activity Is Required for STAT5-Dependent GM-CSF Functional Activity in Macrophages and Differentiation to Dendritic Cells

Sebastián

Serra

Yeramian

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

After interaction with its receptor, GM-CSF induces phosphorylation of the β-chain in two distinct domains in macrophages. One induces activation of mitogen-activated protein kinases and the PI3K/Akt pathway, and the other induces JAK2-STAT5. In this study we describe how trichostatin A (TSA), which inhibits deacetylase activity, blocks JAK2-STAT5-dependent gene expression but not the expression of genes that depend on the signal transduction induced by the other domain of the receptor. TSA treatment inhibited the GM-CSF-dependent proliferation of macrophages by interfering with c-myc and cyclin D1 expression. However, M-CSF-dependent proliferation, which requires ERK1/2, was unaffected. Protection from apoptosis, which involves Akt phosphorylation and p21waf-1 expression, was not modified by TSA. GM-CSF-dependent expression of MHC class II molecules was inhibited because CIITA was not induced. The generation of dendritic cells was also impaired by TSA treatment because of the inhibition of IRF4, IRF2, and RelB expression. TSA mediates its effects by preventing the recruitment of RNA polymerase II to the promoter of STAT5 target genes and by inhibiting their expression. However, this drug did not affect STAT5A or STAT5B phosphorylation or DNA binding. These results in GM-CSF-treated macrophages reveal a relationship between histone deacetylase complexes and STAT5 in the regulation of gene expression.

show abstract

Defective development of splenic and epidermal CD4⁺dendritic cells in mice deficient for IFN regulatory factor-2

Cited by 116 publications

References 42 publications

IRF family proteins and type I interferon induction in dendritic cells

IRF family proteins and type I interferon induction in dendritic cells

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

Deacetylase Activity Is Required for STAT5-Dependent GM-CSF Functional Activity in Macrophages and Differentiation to Dendritic Cells

Contact Info

Product

Resources

About

Defective development of splenic and epidermal CD4+dendritic cells in mice deficient for IFN regulatory factor-2

Cited by 116 publications

References 42 publications

IRF family proteins and type I interferon induction in dendritic cells

IRF family proteins and type I interferon induction in dendritic cells

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

Deacetylase Activity Is Required for STAT5-Dependent GM-CSF Functional Activity in Macrophages and Differentiation to Dendritic Cells

Contact Info

Product

Resources

About

Defective development of splenic and epidermal CD4⁺dendritic cells in mice deficient for IFN regulatory factor-2