Upon Prolonged Allergen Exposure IL-4 and IL-4Rα Knockout Mice Produce Specific IgE Leading to Anaphylaxis

Grünewald, Susanne; Teufel, Martin; Erb, Klaus J.; Nelde, Annette; Mohrs, Markus; Brombacher, Frank; Bröcker, Eva B.; Sebald, Walter; Duschl, Albert

doi:10.1159/000053833

Cited by 22 publications

(18 citation statements)

References 22 publications

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“…The relatively strong induction of anti-IgEmediated PCA responses in association with only marginal increases in serum IgE following immunization is consistent with observations that even low level IgE receptor occupancy can support the degranulation of basophils (62,63) or mast cells (43). The increased IgE levels and effector responses following immunization confirm and extend previous reports of OVA-induced anaphylactic responses in IL-4R␣ Ϫ/Ϫ mice (19), by indicating that neither IL-4 nor IL-13 is absolutely required for IgE production or for IgE-dependent mast cell activation in vivo. These observations suggest the existence of an additional pathway to IgE, the exact nature of which remains to be elucidated.…”

Section: Discussionsupporting

confidence: 89%

“…Cross-linking mast cell-bound IgE triggers degranulation and downstream effector function, including anaphylactic reactions. Such responses have been described in mice lacking IL-4R␣ (19), indicating that IgE effector function could be elicited in animals that lack responsiveness to either IL-4 or IL-13. Nevertheless, the use of OVA rather than anti-IgE to trigger the response leaves some question as to its IgE dependence.…”

Section: Ige Generation and Mast Cell Effector Function In Micementioning

confidence: 86%

“…Mice deficient in both IL-4 and IL-13, those lacking IL-4R␣, and those deficient in STAT6 would be expected to lack IgE completely, and most studies investigating serum IgE levels support this prediction (29,(45)(46)(47). Surprisingly, however, IgE has been detected in IL-4R␣ knockout mice following immunization with OVA (19) and in STAT6-deficient animals infected with MAIDS (23), suggesting that under some conditions, IgE could be produced independently of IL-4 and IL-13.…”

Section: Discussionmentioning

confidence: 99%

“…Even more intriguing are observations that suggest IgE can be made in the absence of both IL-4 and IL-13, or in the absence of their shared signaling elements. Infection with MAIDS induces IgE in STAT6-deficient mice (23), and IL-4R␣-deficient mice generate a serum IgE response, albeit weak and delayed, following immunization with OVA (19). Based on these observations, it is conceivable that additional pathway(s) exists to generate this important effector molecule.…”

Section: Ige Generation and Mast Cell Effector Function In Micementioning

confidence: 99%

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IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13

Fish¹,

Donaldson²,

Goldman³

et al. 2005

The Journal of Immunology

104

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IL-4 and IL-13 are potent cytokines that drive production of IgE, which is critical to the development of atopic disease. In this study, we directly compared IgE generation and IgE-dependent mast cell effector function in mouse strains lacking IL-4, IL-13, IL-4 + IL-13, or their common receptor component, IL-4Rα. Although serum IgE was undetectable under resting conditions in most animals deficient in one or both cytokines, peritoneal mast cells from mice lacking IL-4 or IL-13 had only partial reductions in surface IgE level. In contrast, peritoneal mast cells from IL-4/13−/− and IL-4Rα−/− animals were severely deficient in surface IgE, and showed no detectable degranulation following treatment with anti-IgE in vitro. Surprisingly, however, intradermal challenge with high concentrations of anti-IgE Ab induced an ear-swelling response in these strains, implying some capacity for IgE-mediated effector function in tissue mast cells. Furthermore, upon specific immunization with OVA, both IL-4/IL-13−/− and IL-4Rα−/− mice produced detectable levels of serum IgE and Ag-specific IgG1, and generated strong ear-swelling responses to intradermal administration of anti-IgE. These findings suggest that a mechanism for IgE production exists in vivo that is independent of IL-4 or IL-13.

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Section: Discussionsupporting

confidence: 89%

Section: Ige Generation and Mast Cell Effector Function In Micementioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Ige Generation and Mast Cell Effector Function In Micementioning

confidence: 99%

See 2 more Smart Citations

IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13

Fish¹,

Donaldson²,

Goldman³

et al. 2005

The Journal of Immunology

104

View full text Add to dashboard Cite

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“…A modified immunization protocol was used (20). Pinworminfected and noninfected mice were immunized intraperitoneally on days 14 and 21 with 50 g grade V chicken egg Ova (Sigma-Aldrich) and 1.3% aluminum hydroxide (Imject alum; Pierce) suspended in PBS to a total volume of 200 l. Nonimmunized control mice received only PBS plus alum.…”

Section: Mice Gamma Interferon Receptor-deficient (Ifn-␥rmentioning

confidence: 99%

Infection withSyphacia obvelata(Pinworm) Induces Protective Th2 Immune Responses and Influences Ovalbumin-Induced Allergic Reactions

et al. 2006

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Infections with pinworms are common in rodent animal facilities. In this study, we show the consequence of an outbreak in a transgenic barrier facility of infection by Syphacia obvelata, a murine pinworm gastrointestinal nematode. Immune responses were defined in experimental infection studies with BALB/c mice. Infection with S. obvelata induced a transient Th2-type immune response with elevated interleukin 4 (IL-4), IL-5, and IL-13 cytokine production and parasite-specific immunoglobulin G1 (IgG1). In contrast, BALB/c mice deficient in IL-13, IL-4/13, or the IL-4 receptor alpha chain showed chronic disease, with a >100-fold higher parasite burden, increased gamma interferon production, parasite-specific IgG2b, and a default Th2 response. Interestingly, infected IL-4 ؊/؊ BALB/c mice showed only slightly elevated parasite burdens compared to the control mice, suggesting that IL-13 plays the dominant role in the control of S. obvelata. The influence that pinworm infection has on the allergic response to a dietary antigen was found to be important. Helminth-infected mice immunized against ovalbumin (Ova) elicited more severe anaphylactic shock with reduced Ova-specific IL-4 and IL-5 than did noninfected controls, demonstrating that S. obvelata infection is able to influence nonrelated laboratory experiments. The latter outcome highlights the importance of maintaining mice for use as experimental models under pinworm-free conditions.

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STAT6‐dependent and ‐independent mechanisms in Th2 polarization

2012

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Th2 cells play a key role in directing immune responses against helminths. Additionally, Th2 cells are crucial for many types of allergic reactions. Whereas the molecular mechanisms underlying the differentiation of other types of Th cells are well understood, Th2 differentiation is still a controversial topic. IL-4 and its downstream transcription factor signal transducer and activator of transcription (STAT)6 are well-known key mediators in Th2 differentiation. The fact that Th2 cells themselves are the most potent source of IL-4 suggests that additional mechanisms promoting the initiation of Th2 differentiation exist. This article gives an overview on STAT6-dependent and -independent mechanisms involved in the process of Th2 polarization, including Notch, mTORC2, IL-2/STAT5, and Wnt. Furthermore, we emphasize the role of STAT6 not only as a transcriptional activator promoting Th2 development, but also in fine-tuning alternative signaling pathways which are involved in the initiation of Th2 polarization.

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Upon Prolonged Allergen Exposure IL-4 and IL-4Rα Knockout Mice Produce Specific IgE Leading to Anaphylaxis

Cited by 22 publications

References 22 publications

IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13

IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13

Infection withSyphacia obvelata(Pinworm) Induces Protective Th2 Immune Responses and Influences Ovalbumin-Induced Allergic Reactions

STAT6‐dependent and ‐independent mechanisms in Th2 polarization

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