Reversal of human allergen-specific CRTH2+ TH2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide

Annunziato, Francesco; Cosmi, A. Lorenzo; Manetti, Roberto; Brugnolo, Francesca; Parronchi, Paola; Maggi, Enrico; Nagata, Kazuhiro; Romagnani, Sergio

doi:10.1067/mai.2001.119156

Cited by 41 publications

(26 citation statements)

References 23 publications

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“…In addition, T-bet also downregulated the expression of CRTH2, which is generally accepted as a T H 2-associated marker. 23,24 Interestingly, CCR4 was not downregulated (not shown) in agreement with recent data demonstrating the coexpression of CCR4 and CXCR3, 25 particularly in skin-infiltrating T H 1 cell populations, 26 such as those involved in psoriasis. 27 This notion was further supported by the fact that T-betetransfected T H 2 cells readily migrated in vitro in response to CXCR3 ligands (Fig 6, C) without losing CCR4 responsiveness (not shown).…”

Section: Discussionsupporting

confidence: 91%

Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities☆

Lametschwandtner

Biedermann

Schwärzler

et al. 2004

Journal of Allergy and Clinical Immunology

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Section: Discussionsupporting

confidence: 91%

Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities☆

Lametschwandtner

Biedermann

Schwärzler

et al. 2004

Journal of Allergy and Clinical Immunology

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“…In contrast, as Figure 3A also shows, the CCL3-5 receptor, CCR5, was expressed on a significantly higher percentage of Th1-than Th2-skewed cells (P Ͻ .001). As reported, 18,33,35 neither marker was expressed on the surface of unstimulated, naive Th cells (data not shown). Figure 3B shows that the frequencies of CRTH2-and IL-4-expressing Th cells in these cultures were significantly correlated and both inversely correlated with those of IFN-␥-producing cells.…”

Section: Gata-3 and T-bet In Crth2-expressing Th Cells 4345mentioning

confidence: 68%

“…46 It is conceivable that analogous differences in the cis-trans interactions at the Th2 cytokine gene locus and other loci may account for experimental findings quite unique to human Th cells, such as a low level of phenotype stability and an increased propensity to switch phenotypes or accommodate intermediate phenotypes in response to developmental signals. 31,33,35,39 Our study, by highlighting species-specific features in the regulation of GATA-3 expression, further defines the phenotype of human Th2 cells. Our findings do not downplay the importance of this factor in Th-cell physiology.…”

Section: Discussionmentioning

confidence: 99%

GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells

Fanis

Mori

Kurnat

et al. 2007

Blood

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GATA-3 and T-box expressed in T cells (T-bet) play central roles in IntroductionT-cell receptor (TCR) ligation by the peptide-major histocompatibility complex (MHC) class II induces the clonal expansion of naive Th cells and their differentiation into at least 2 subtypes of effector cells: Th1, which produces IFN-␥ and plays a crucial role in immune responses against intracellular pathogens, and Th2, which expresses IL-4, IL-5, and IL-13 and is involved in antibody (Ab)-mediated responses to extracellular parasites. An imbalance in the relative proportion and function of either Th-cell population-as determined by the complex interaction of the genetic background and environmental factors, including exposure to certain infectious agents-has been implicated in the development of abnormal immune responses and the onset of autoimmune and allergic conditions (reviewed by Wills-Karp et al 1 ).Besides the intrinsic predisposition of naive Th cells to acquire a Th1 or Th2 phenotype, which is thought to be controlled by genetic and stochastic variables, a host of extrinsic factors influences Th-cell differentiation through the regulation of dendriticcell function, and thereby the antigen load, and the exposure to polarizing costimulatory signals and cytokines (eg, IL-12). 2,3 Transcriptional and epigenetic mechanisms play eminent roles in the coordinate regulation of the molecular programs that bring to selective activation or repression of Th-cell-polarized genes. Specifically, T-box expressed in T cells (T-bet), also known as T-box 21 (Tbx21), plays a central role in Th1-cell development and selectively induces the expression of such Th1-restricted genes as IFN-␥ and the ␤ subunit of the IL-12 receptor (IL-12R␤) (reviewed by Szabo et al 4 ). Conversely, GATA-3 has been characterized as the master switch factor for Th2 cells, because it induces, by different mechanisms, the coordinate activation of the IL-4, IL-5, and IL-13 genes. 5 At least as importantly, T-bet and GATA-3 contribute to the definition of a stable (ie, inheritable) polarized cytokine phenotype, also by promoting the irreversible silencing of type 2 and type 1 genes, respectively. [3][4][5] In line with this notion, studies of in vitro-polarized murine Th cells have consistently documented the selective transcription of the T-bet and GATA-3 genes in Th1 and Th2 cells, respectively. [6][7][8] Thus, these genes appear to be subject to tight regulation by developmental signals, particularly those delivered through the IL-12 and IL-4 receptors. Their expression pattern has rapidly become an integral part of the "Th1/Th2 paradigm" and a surrogate marker of polarization in studies of Th-cell phenotype, function, and involvement in human disease. [9][10][11][12] In this context, over the past decade much attention has focused on the possibility that Th-cell polarization might be reflected in the surface phenotype as well, a notion carrying both conceptual and practical implications. A few recent studies have identified certain chemoattractant receptors as being...

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“…Of note, IL-12 produced by DCs in response to CpG-containing ODNs was found to be able to induce IFN-c production even by established allergen-specific Th2 effectors through the upregulation on their surface of the IL-12Rb2 chain (63). Of note, even more pronounced immune deviation from Th2 to Th1 in the allergen-specific response was observed by using allergen : CpG-ODNs conjugates (64).…”

Section: Possible Regulation Of Th2-mediated Inflammation By Immune Dmentioning

confidence: 93%

Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?

Romagnani

2005

Allergy

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Several recent data suggest the importance of different types of cells in the regulation of T‐cell effector‐mediated immune responses. However, a unique specific marker for these cells has not yet been identified. Moreover, in addition to a dedicated functional lineage, even a ‘plastic’ phenotype of regulatory T cells seems to exist. The lack of a unique specific marker for regulatory T cells, as well as their heterogeneity, make it difficult to determine whether a defect of regulatory T cells plays a role in the pathogenesis of common allergic disorders. Novel therapeutic strategies based on the induction or potentiation of regulatory T cells able to hamper allergic inflammatory reactions are desirable, but their possible efficacy and safety are not yet known. At present, therapeutic strategies able to induce an immune deviation of allergen‐specific type 2 T‐helper responses to a less polarized phenotype rather than a general immune suppression appear more realistic.

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Reversal of human allergen-specific CRTH2+ TH2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide

Cited by 41 publications

References 23 publications

Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities☆

Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities☆

GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells

Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?

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