Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcϵRI

Okumura, Shigeru; Kashiwakura, Jun‐ichi; Tomita, Hisashi; Matsumoto, Kenji; Nakajima, Toshiharu; Saito, Hirohisa; Okayama, Yoshimichi

doi:10.1182/blood-2002-12-3929

Cited by 138 publications

(127 citation statements)

References 35 publications

(46 reference statements)

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“…Interestingly, mast cells primed in the presence of IL-4 produced even higher levels of CCL1, raising the interesting hypothesis that a "local Th2 environment" further primes mast cells for CCL1 production. These data support previous observations in both murine and human mast cells that CCL1 is the most abundant chemokine produced after IgE cross-linking (32)(33)(34).…”

Section: Discussionsupporting

confidence: 82%

Coordinated Involvement of Mast Cells and T Cells in Allergic Mucosal Inflammation: Critical Role of the CC Chemokine Ligand 1:CCR8 Axis

Gonzalo

Qiu

Lora

et al. 2007

The Journal of Immunology

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CCL1 is the predominant chemokine secreted from IgE-activated human and mouse mast cells in vitro, colocalizes to mast cells in lung biopsies, and is elevated in asthmatic airways. CCR8, the receptor for CCL1, is expressed by ∼70% of CD4+ T lymphocytes recruited to the asthmatic airways, and the number of CCR8-expressing cells is increased 3-fold in the airways of asthmatic subjects compared with normal volunteers. In vivo, CCL1 expression in the lung is reduced in mast cell-deficient mice after aeroallergen provocation. Neutralization of CCL1 or CCR8 deficiency results in reduced mucosal lung inflammation, airway hyperresponsiveness, and mucus hypersecretion to a similar degree as detected in mast cell-deficient mice. Adenoviral delivery of CCL1 to the lungs of mast cell-deficient mice restores airway hyperresponsiveness, lung inflammation, and mucus hypersecretion to the degree observed in wild-type mice. The consequences of CCR8 deficiency, including a marked reduction in Th2 cytokine levels, are comparable with those observed by depletion of CD4+ T lymphocytes. Thus, mast cell-derived CCL1- and CCR8-expressing CD4+ effector T lymphocytes play an essential role in orchestrating lung mucosal inflammatory responses.

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Section: Discussionsupporting

confidence: 82%

Coordinated Involvement of Mast Cells and T Cells in Allergic Mucosal Inflammation: Critical Role of the CC Chemokine Ligand 1:CCR8 Axis

Gonzalo

Qiu

Lora

et al. 2007

The Journal of Immunology

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“…Human monocytes were separated as described previously (30). The final purity of monocytes was Ͼ95%.…”

Section: Purification Of Human Peripheral Blood Monocytesmentioning

confidence: 99%

“…Isolation of total RNA and real-time quantitative RT-PCR for OX40L, 4-1BBL, and GAPDH were performed as described previously (30). Relative expression levels were determined using cycle threshold values and the Compared Ct method to adjust for coamplified housekeeper gene levels, 2-fold amplification/cycle rates, and the reference expression level of control samples (32).…”

Section: Isolation Of Rna and Real-time Quantitative Rt-pcrmentioning

confidence: 99%

T Cell Proliferation by Direct Cross-Talk between OX40 Ligand on Human Mast Cells and OX40 on Human T Cells: Comparison of Gene Expression Profiles between Human Tonsillar and Lung-Cultured Mast Cells

Kashiwakura

Yokoi

Saito

et al. 2004

The Journal of Immunology

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Mast cells (MCs) are the primary effector cells in allergic reactions and have also been found to activate T cells and to reside in close physical proximity to T cells. However, the molecular mechanisms involved in the MC-T cell interaction remain unclear. We hypothesized that human tonsillar MCs, which locate in the interfollicular areas, might interact with T cells. Thus, we first established a culture system of human tonsillar MCs and then compared gene expression profiles of tonsillar MCs with that of lung MCs before and after aggregation of FcεRI by using high-density oligonucleotide probe arrays. Here we show that resting tonsillar MCs, when compared with lung MCs, revealed significantly higher expression levels for CC chemokines (CCL3 and 4), which recruit T cells, and for TNFR superfamilies (OX40 ligand and 4-1BB ligand), which induce proliferation of T cells. After aggregation of FcεRI, not only tonsillar MCs but also lung MCs up-regulated the expression of these molecules. We confirmed that T cell proliferation is induced in direct cross-talk by the MC surface molecule OX40 ligand. These results suggest that human MCs may play important roles in adaptive immunity through the T cell responses.

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“…TLR4 was shown to be a receptor for LPS (18,19). Recent studies on mouse (20)(21)(22) and human (23) mast cells suggested that LPS-induced activation was mediated through TLR4 expressed on mast cells. A protective role for mast cells in bacterial infection was first addressed in a bacterial peritonitis animal model, and the infection was suggested to be mediated by the production of TNF␣ as a consequence of TLR4 activation (21,24,25).…”

mentioning

confidence: 99%

Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function

Nigo¹,

Yamashita²,

Hirahara³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

136

135

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In a mouse experimental asthma model, the administration of bacterial lipopolysaccharide (LPS), particularly at low doses, enhances the levels of ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify the cellular and molecular basis for the LPS effect, we demonstrate that the OVA-induced eosinophilic inflammation in the lung is dramatically increased by the administration of LPS in wild-type mice, whereas such increase was not observed in mast-cell-deficient mice or Toll-like receptor (TLR)4-deficient mice. Adoptive transfer of bone-marrow-derived mast cells (BMMCs) from wild-type, but not from TLR4-deficient, mice restored the increased eosinophilic inflammation in mast-celldeficient mice. Wild-type BMMCs pretreated with LPS in vitro also reconstituted the eosinophilic inflammation. Moreover, in vitro analysis revealed that the treatment of BMMCs with LPS resulted in NF-B activation, sustained up-regulation of GATA1 and -2 expression, and increased the capability to produce IL-5 and -13. Dramatic increases in the expression of IL-5 and -13 and Eotaxin 2 were detected in LPS-treated BMMCs after costimulation with LPS and IgE͞Ag. Overexpression of GATA1, but not GATA2, in MC9 mast cells resulted in increased transcriptional activity of IL-4, -5, and -13. Furthermore, the levels of transcription of Th2 cytokines in BMMCs were decreased by the introduction of small interfering RNA for GATA1. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 and subsequent increase in Th2 cytokine production.cytokine ͉ GATA1 ͉ mast cell ͉ lipopolysaccharide ͉ bone-marrow-derived mast cells

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Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcϵRI

Cited by 138 publications

References 35 publications

Coordinated Involvement of Mast Cells and T Cells in Allergic Mucosal Inflammation: Critical Role of the CC Chemokine Ligand 1:CCR8 Axis

Coordinated Involvement of Mast Cells and T Cells in Allergic Mucosal Inflammation: Critical Role of the CC Chemokine Ligand 1:CCR8 Axis

T Cell Proliferation by Direct Cross-Talk between OX40 Ligand on Human Mast Cells and OX40 on Human T Cells: Comparison of Gene Expression Profiles between Human Tonsillar and Lung-Cultured Mast Cells

Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function

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