Functional Expression of IL-12 Receptor by Human Eosinophils: IL-12 Promotes Eosinophil Apoptosis

Nutku, Esra; Zhuang, Qianli; Gounni, Abdelilah Soussi; Aris, Fadi; Mazer, Bruce; Hamid, Qutayba

doi:10.4049/jimmunol.167.2.1039

Cited by 31 publications

(27 citation statements)

References 47 publications

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“…However, local administration of exogenous IP10 in the present studies in sensitized and challenged mice increased the allergic response in the lung and airway along with increased IL-4, IL-5, and IL-13 levels. Together, these data suggest an increase in the activation or recruitment of Th2 type cells into the lung (41). Interestingly, airway hyperreactivity was significantly reduced at early time points following instillation of IP10 with allergen, but subsequently resulted in increased airway hyperreactivity and eosinophil accumulation.…”

Section: Cd3mentioning

confidence: 71%

Differential Role of IFN-γ-Inducible Protein 10 kDa in a Cockroach Antigen-Induced Model of Allergic Airway Hyperreactivity: Systemic Versus Local Effects

Thomas

Kunkel

Lukacs

2002

The Journal of Immunology

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The ability of IFN-γ to antagonize established Th2 type allergic responses is well documented. To investigate the role of IFN-γ-inducible protein 10 kDa (IP10) in the allergic response, we chose to investigate the effect of IP10 neutralization on an established Th2 response. Systemic neutralization of IP10 at the time of allergen challenge increased airway hyperreactivity as well as airway eosinophil accumulation. Interestingly, IFN-γ levels were markedly reduced in both the lung and peripheral lymph node following IP10 neutralization. Furthermore, the number of CXCR3+CD4+ T cells was decreased in the peripheral lymph node following neutralization of IP10. Introduction of exogenous IP10 into the airway at the time of allergen challenge also dramatically increased eosinophil accumulation in the airway. Protein levels of IL-4, IL-5, and IL-13 were significantly increased in the lung following exogenous airway administration of IP10 with allergen. Interestingly, airway hyperreactivity was significantly decreased at early time points following concurrent IP10 and allergen challenge but rebounded at 24 and 48 h post allergen challenge. Although IP10 may initially be acting locally to dampen the allergic response, its ability to recruit eosinophils may ultimately supersede any immunomodulatory effect it may have in an established allergic response. These results suggest that while systemic levels of IP10 are beneficial in controlling the allergic response, possibly by regulating cellular trafficking in the lymph node, local administration of exogenous IP10 into an established allergic response may be detrimental.

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Section: Cd3mentioning

confidence: 71%

Differential Role of IFN-γ-Inducible Protein 10 kDa in a Cockroach Antigen-Induced Model of Allergic Airway Hyperreactivity: Systemic Versus Local Effects

Thomas

Kunkel

Lukacs

2002

The Journal of Immunology

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“…Cell types other than NK cells may respond to the combination of IL-12 and immobilized IgG. Granulocytes and monocytes both express FcR for IgG and these cell populations have also been shown to express the IL-12R (34,35). Thus, the response to IL-12R and FcR triggering in vivo could be influenced by the activity of these other cell compartments.…”

Section: Resultsmentioning

confidence: 99%

Src Homology 2–Containing Inositol 5′-Phosphatase 1 Negatively Regulates IFN-γ Production by Natural Killer Cells Stimulated with Antibody-Coated Tumor Cells and Interleukin-12

Parihar¹,

Trotta²,

Roda³

et al. 2005

Cancer Research

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We have previously shown that natural killer (NK) cells secrete a distinct profile of immunomodulatory cytokines in response to dual stimulation with antibody-coated tumor cells and interleukin-12 (IL-12). This NK cell cytokine response is dependent on synergistic signals mediated by the activating receptor for the Fc portion of IgG (Fc;RIIIa) and the IL-12 receptor (IL-12R), both constitutively expressed on NK cells. The phosphatase Src homology 2-containing inositol 5V -phosphatase 1 (SHIP1) is known to exert inhibitory effects on Fc receptor (FcR) signaling via its enzymatic activity on phosphatidylinositol 3-kinase (PI3-K) products within many cells of the immune system, most notably mast cells, B cells, and monocytes. However, its activity in the context of FcR activation on NK cells has not been fully explored. The current study focused on the regulation of Fc;RIIIa-induced NK cell cytokine production by SHIP1. Inhibitor studies showed that NK cell IFN-; production following FcR stimulation in the presence of IL-12 depended, in part, on the downstream products of PI3-K. Overexpression of wild-type (WT) SHIP1, but not a catalytic-deficient mutant, via retroviral transfection of primary human NK cells, resulted in a >70% reduction of NK cell IFN-; production in response to costimulation. In addition, NK cells from SHIP1

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“…It has been shown to inhibit allergen-induced airway hyperreactivity and eosinophil accumulation after allergen challenge as well as decrease levels of the Th2 cytokines, IL-4 and IL-5 (31,42). In addition, IL-12 has been linked to eosinophil apoptosis (43). IL-12 induces the production of IFN-␥, which then induces the production of several type 1 mediators, including the CXCR3 ligands, CXCL9 and CXCL10 (44).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Cockroach Antigen-Induced Allergic Airway Hyperreactivity by the CXCR3 Ligand CXCL9

Thomas

Kunkel

Lukacs

2004

The Journal of Immunology

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Allergic airway disease is characterized by a robust lymphocytic infiltrate, elaboration of Th2-type inflammatory mediators, pulmonary eosinophil accumulation, and airway hyperreactivity. The CXCR3 ligands, CXCL9 (monokine induced by IFN-γ) and CXCL10 (IFN-inducible protein, 10 kDa), are IFN-γ-inducible, Th1-type chemokines. As CXCL10 has been previously shown to participate in the modulation of allergic inflammation, we were interested in investigating the possible role that CXCL9 may play in this inflammatory response. Expression of CXCL9 was primarily identified in airway epithelial cells by immunohistochemical staining. Airway neutralization of CXCL9 at the time of allergen challenge significantly increased airway hyperreactivity, airway eosinophil accumulation, and IL-4 levels in the bronchoalveolar lavage while significantly decreasing airway levels of IL-12. In contrast, introduction of exogenous CXCL9 into the airway at the time of allergen challenge dramatically reduced airway hyper-reactivity and eosinophil accumulation. Moreover, pulmonary levels of IL-4 were significantly reduced, whereas levels of IL-12 were significantly increased, with exogenous CXCL9 treatment. In lymphocytes restimulated with CXCL9 and allergen in vitro, CXCL9 down-regulated IL-4 expression and up-regulated IFN-γ expression, suggesting that CXCL9 is able to direct activated lymphocytes toward a Th1-type phenotype. Additionally, CXCL9 was shown to inhibit CC chemokine ligand 11-induced eosinophil chemotaxis in in vitro assays. Taken together, our results demonstrate that the CXCR3 ligand CXCL9 is involved in regulation of the allergic response in the lung by regulation of lymphocyte activation and eosinophil recruitment.

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Functional Expression of IL-12 Receptor by Human Eosinophils: IL-12 Promotes Eosinophil Apoptosis

Cited by 31 publications

References 47 publications

Differential Role of IFN-γ-Inducible Protein 10 kDa in a Cockroach Antigen-Induced Model of Allergic Airway Hyperreactivity: Systemic Versus Local Effects

Differential Role of IFN-γ-Inducible Protein 10 kDa in a Cockroach Antigen-Induced Model of Allergic Airway Hyperreactivity: Systemic Versus Local Effects

Src Homology 2–Containing Inositol 5′-Phosphatase 1 Negatively Regulates IFN-γ Production by Natural Killer Cells Stimulated with Antibody-Coated Tumor Cells and Interleukin-12

Regulation of Cockroach Antigen-Induced Allergic Airway Hyperreactivity by the CXCR3 Ligand CXCL9

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