Interleukin‐4‐independent production of Th2 cytokines by nasal lymphocytes and nasal eosinophilia in murine allergic rhinitis

Satoskar, A. R.; Abe, Mie; Harn, D. A.; Okano, Mitsuhiro; Nishizaki, Kazunori; Takeda, Yoshifumi; Yoshino, Tadashi; Brombacher, Frank; Satoskar, A. A.

doi:10.1034/j.1398-9995.2000.00429.x

Cited by 30 publications

(25 citation statements)

References 29 publications

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“…Thus, our results indicate that signals mediated by CRTH2 selectively enhance Th2-type Ab production. The decreased production of IL-4 by submandibular lymph node cells from CRTH2 Ϫ/Ϫ mice in response to Cry j 1 restimulation supports this result because IL-4 plays a critical role in IgE synthesis in vivo (37). Although whether CRTH2 activation directly leads to IL-4 production in mice remains unclear, recent investigations have demonstrated that PGD 2 causes the preferential induction of IL-4 production by Th2 cells in humans by binding to CRTH2 (38,39).…”

Section: Discussionsupporting

confidence: 56%

CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice

Nomiya

Okano

Fujiwara

et al. 2008

The Journal of Immunology

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PGD2 is the major prostanoid produced during the acute phase of allergic reactions. Two PGD2 receptors have been isolated, DP and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), but whether they participate in the pathophysiology of allergic diseases remains unclear. We investigated the role of CRTH2 in the initiation of allergic rhinitis in mice. First, we developed a novel murine model of pollinosis, a type of seasonal allergic rhinitis. Additionally, pathophysiological differences in the pollinosis were compared between wild-type and CRTH2 gene-deficient mice. An effect of treatment with ramatroban, a CRTH2/T-prostanoid receptor dual antagonist, was also determined. Repeated intranasal sensitization with Cry j 1, the major allergen of Cryptomeria japonica pollen, in the absence of adjuvants significantly exacerbated nasal hyperresponsive symptoms, Cry j 1-specific IgE and IgG1 production, nasal eosinophilia, and Cry j 1-induced in vitro production of IL-4 and IL-5 by submandibular lymph node cells. Additionally, CRTH2 mRNA in nasal mucosa was significantly elevated in Cry j 1-sensitized mice. Following repeated intranasal sensitization with Cry j 1, CRTH2 gene-deficient mice had significantly weaker Cry j 1-specific IgE/IgG1 production, nasal eosinophilia, and IL-4 production by submandibular lymph node cells than did wild-type mice. Similar results were found in mice treated with ramatroban. These results suggest that the PGD2-CRTH2 interaction is elevated following sensitization and plays a proinflammatory role in the pathophysiology of allergic rhinitis, especially pollinosis in mice.

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Section: Discussionsupporting

confidence: 56%

CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice

Nomiya

Okano

Fujiwara

et al. 2008

The Journal of Immunology

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“…The IL-5 producers outnumbered the IL-4 producers, consistent with the fact that these cytokines are frequently not coexpressed by T cells (47,48). This dissociation of "Th2" cytokines is not surprising because IL-4 and IL-5 expression by T cells underlies independent instructed differentiation and different gene regulation pathways (48,49).…”

Section: Discussionmentioning

confidence: 72%

Dissociation of Experimental Allergic Encephalomyelitis Protective Effect and Allergic Side Reactions in Tolerization with Neuroantigen

Lichtenegger

Küerten

Faas

et al. 2007

The Journal of Immunology

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Administration of autoantigens under conditions that induce type 2 immunity frequently leads to protection from T cell-mediated autoimmune diseases. Such treatments, however, are inherently linked to the induction of IgG1 Abs and to the risk of triggering anaphylactic reactions. We studied the therapeutic benefit vs risk of immune deviation in experimental allergic encephalomyelitis of SJL mice induced by MP4, a myelin basic protein-proteolipid protein (PLP) fusion protein. MP4 administration in IFA induced type 2 T cell immunity, IgG1 Abs, and experimental allergic encephalomyelitis protection, and all three were enhanced by repeat injections. Despite high Ab titers, anaphylactic side reactions were not observed when MP4 was repeatedly injected in IFA or as soluble Ag s.c. In contrast, lethal anaphylaxis was seen after s.c. injection of soluble PLP:139–151 peptide, but not when the peptide was reinjected in IFA. Therefore, the Ab response accompanying the immune therapy constituted an anaphylactic risk factor only when the autoantigen was not retained in an adjuvant and when it was small enough to be readily disseminated within the body. Taken together, our data show that treatment regimens can be designed to boost the protective type 2 T cell response while avoiding the risk of Ab-mediated allergic side effects.

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“…Early interleukin (IL)-4 and thymic stromal lymphopoietin (TSLP) produced by basophils in response to allergens with protease activity may contribute to Th2 differentiation [12]. Th2 cells produce IL-4/IL-13 and express CD40L, which promote the class-switching of B cells to immunoglobulin (Ig)E [13,14]. When sensitized subjects inhale antigens, the antigens pass through the epithelial tight junctions in the nasal mucosa to bind IgE on the surface of mast cells in the epithelial layer of the nasal mucosa, inducing the release of chemical mediators including histamine, prostaglandins and cysLTs by aggregation of FceRI.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis

Okano

2009

Clinical and Experimental Immunology

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SummaryAllergic rhinitis is a common airway disease characterized by hypersensitivity, exudation, hypersecretion, inflammatory cell infiltration and remodelling. Intranasal glucocorticosteroids are the most effective drugs for controlling the inflammation caused by allergic rhinitis. Glucocorticosteroids exert anti-inflammatory effects through at least two pathways: the transactivation pathway and the transrepression pathway. Glucocorticosteroids also exert regulatory functions by inducing regulatory cytokines and forkhead box P3 (FoxP3 + ) regulatory T cells. Evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1 receptor antagonists, intranasal glucocorticosteroids can improve impaired performance symptoms, such as daytime sleepiness, associated with allergic rhinitis. Recent studies suggest that intranasal glucocorticosteroids might also be useful for the prophylactic treatment of pollinosis; this possibility is supported by the molecular mechanism of the anti-inflammatory action of glucocorticosteroids. These findings suggest that intranasal glucocorticosteroids might be positioned as first-line drugs for the treatment of both perennial and seasonal allergic rhinitis.

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Interleukin‐4‐independent production of Th2 cytokines by nasal lymphocytes and nasal eosinophilia in murine allergic rhinitis

Abstract: These results indicate that although IL-4 is necessary for the production of Th2-associated antibodies--in particular, IgE--it is not required for either the production of the Th2-associated cytokines IL-5 and IL-10, or the induction of nasal eosinophilia.

Cited by 30 publications

References 29 publications

CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice

CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice

Dissociation of Experimental Allergic Encephalomyelitis Protective Effect and Allergic Side Reactions in Tolerization with Neuroantigen

Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis

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