A Second Amplifier Function for the Allergy-Associated FcεRI-β Subunit

Donnadieu, Emmanuel; Jouvin, Marie-Hélène; Kinét, Jean-Pierre

doi:10.1016/s1074-7613(00)80203-4

Cited by 147 publications

(160 citation statements)

References 51 publications

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“…For example, loss of Fc⑀RI ␤ should reduce competition for the ␥ subunit (55)(56)(57)(58). Accordingly, we have observed increased Fc␥RIII expression and signaling coincidental with Fc⑀RI down-regulation (63).…”

Section: Discussionmentioning

confidence: 91%

“…Accordingly, we have observed increased Fc␥RIII expression and signaling coincidental with Fc⑀RI down-regulation (63). Kinet's laboratory convincingly showed that Fc⑀RI ␤ amplifies both the expression and signaling of the IgE receptor (55)(56)(57)(58). Given the novel role of the ␤-chain as an Fc⑀RI amplifier and the presence of ␤-chain polymorphisms in FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

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IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

Gillespie

DeMartino

Zhu

et al. 2004

The Journal of Immunology

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FcεRI expression and function is a central aspect of allergic disease. Using bone marrow-derived mouse mast cell populations, we have previously shown that the Th2 cytokine IL-4 inhibits FcεRI expression and function. In the current study we show that the Th2 cytokine IL-10 has similar regulatory properties, and that it augments the inhibitory effects of IL-4. FcεRI down-regulation was functionally significant, as it diminished inflammatory cytokine production and IgE-mediated FcεRI up-regulation. IL-10 and IL-4 reduced FcεRI β protein expression without altering the α or γ subunits. The ability of IL-4 and IL-10 to alter FcεRI expression by targeting the β-chain, a critical receptor subunit known to modulate receptor expression and signaling, suggests the presence of a Th2 cytokine-mediated homeostatic network that could serve to both initiate and limit mast cell effector function.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

Gillespie

DeMartino

Zhu

et al. 2004

The Journal of Immunology

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“…Although a functional receptor is expressed both as a tetramer (αβγ 2 ) and a trimer (αγ 2 ) in humans [8], intracellular signals [9,10] in addition to cell-surface expression [11] have been reported to be amplified significantly by the β-chain, indicating that the β-chain increases the sensitivity of cell activation to stimulation by allergens. Therefore functional inhibition of the β-chain is a reasonable strategy to suppress allergic reaction by raising the threshold of FcεRI-mediated cell activation by decreasing both the intracellular signals and the cell-surface FcεRI expression.…”

Section: Introductionmentioning

confidence: 99%

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

Takahashi

Matsumoto

2005

Biochemical Journal

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The high-affinity IgE receptor FcεRI plays a key role in triggering allergic reactions. We recently reported that human FcεRI β-chain gene expression was down-regulated by a transcription factor, MZF-1, through an element in the fourth intron. In the present study, we found that this transcriptional repression by MZF-1 required FHL3 (four and a half LIM domain protein 3) as a cofactor. Yeast two-hybrid and immunoprecipitation assays demonstrated that FHL3 bound MZF-1 in vitro and in vivo. Overexpression of FHL3 in KU812 cells suppressed the β-chain promoter activity through the element in the fourth intron in an MZF-1-dependent manner. Furthermore, results from pull-down assays and gel-filtration chromatography employing nuclear extracts indicated that MZF-1 and FHL3 formed a complex of high molecular mass with some additional proteins in the nucleus. Granulocyte-macrophage colony-stimulating factor, which was reported to decrease FcεRI expression, induced the accumulation of FHL3 in the nucleus, in accordance with the repressive role of FHL3 in β-chain gene expression.

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“…8 FcεRIß forms part of the tetrameric FcεRI complex (αβγ 2 ) on mast cells and basophils, 9 and plays a central role in both enhancing surface expression of the receptor complex and amplifying the IgE-mediated signal cascade. 12,13 FcεRIß also associates with the low affinity receptor complex for IgG, FcγRIII, on mast cells, 14,15 and has been proposed as an important enhancer of allergic responses mediated through FcγRIII as well as FcεRI. 16 Based on the sequence homology of HTm 4 to CD20 and FcεRIß, together with its cellular distribution, it is likely that HTm 4 will also have a role in signal transduction as part of a multimeric receptor complex on leucocytes.…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of a mouse homologue of the human haematopoietic cell‐specific four‐transmembrane gene HTm₄

2001

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Summary Haematopoietic cell-specific transmembrane-4 (HTm 4 ) is a four-transmembrane protein most closely related to CD20 and the beta subunit of the high affinity receptor for IgE (FcεRIβ). To date, it has only been described in humans, where it is expressed in haematopoietic cells of both myeloid and lymphoid lineages. The function of HTm 4 is unknown; however, as for CD20 and FcεRI-β, it is likely to play a role in signal transduction as part of a multi-subunit cell surface receptor complex. In this study, we report the cDNA cloning and expression distribution of mouse HTm 4 . The deduced mouse HTm 4 protein is of 213 amino acids, and contains four putative transmembrane domains. Mouse HTm 4 shows 62% overall amino acid identity with human HTm 4 ; the transmembrane regions are highly conserved between both species (75% identity), whereas the N-and C-terminal and inter-transmembrane loop regions are more divergent (52%). Interestingly, the N-terminal domain of mouse HTm 4 is predicted to be 23 amino acids shorter, and the C-terminal domain 23 amino acids longer, than that of human HTm 4 . Northern blot and reverse transcriptase (RT)-PCR analysis suggest that mouse HTm 4 mRNA is expressed at low levels only in spleen, bone marrow and peripheral blood leucocytes. This is the first report of the cloning of HTm 4 from a species other than human, and provides important sequence information towards the understanding of the function of this poorly characterized four-transmembrane molecule.

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A Second Amplifier Function for the Allergy-Associated FcεRI-β Subunit

Cited by 147 publications

References 51 publications

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

Cloning and characterization of a mouse homologue of the human haematopoietic cell‐specific four‐transmembrane gene HTm₄

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A Second Amplifier Function for the Allergy-Associated FcεRI-β Subunit

Cited by 147 publications

References 51 publications

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

Cloning and characterization of a mouse homologue of the human haematopoietic cell‐specific four‐transmembrane gene HTm4

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Cloning and characterization of a mouse homologue of the human haematopoietic cell‐specific four‐transmembrane gene HTm₄