IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen

Herrick, Christina A.; Xu, Lan; McKenzie, Andrew N. J.; Tigelaar, Robert E.; Bottomly, Kim

doi:10.4049/jimmunol.170.5.2488

Cited by 92 publications

(88 citation statements)

References 54 publications

(60 reference statements)

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“…Our data are supported by the finding that endogenous IL-13 is necessary for the priming of a Th2 immune response to OVA administered epicutaneously (48) and by the studies of McKenzie et al (49), demonstrating that mice, lacking IL-13, develop blunted Th2 and IgE Ab responses, whereas mice overexpressing IL-13 have increased IgE Ab levels (50). Our data are reminiscent of the model of murine asthma, described by Gelfand and coworkers (51), induced by priming of the immune response through repeated inhalation of OVA.…”

Section: Discussionsupporting

confidence: 79%

IL-13 Regulates the Immune Response to Inhaled Antigens

Padilla

Daley

Chow

et al. 2005

The Journal of Immunology

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The large inhibitory effect of IL-13 blockers on the asthma phenotype prompted us to ask whether IL-13 would play a role in regulating the allergic immune response in addition to its documented effects on structural pulmonary cells. Because IL-13 does not interact with murine T or B cells, but with monocytes, macrophages, and dendritic cells (DCs), we examined the role of IL-13 in the activation of pulmonary macrophages and DCs and in the priming of an immune response to a harmless, inhaled Ag. We found that a majority of cells called “alveolar or interstitial macrophages” express CD11c at high levels (CD11chigh) and are a mixture of at least two cell types as follows: 1) cells of a mixed phenotype expressing DC and macrophage markers (CD11c, CD205, and F4/80) but little MHC class II (MHC II); and 2) DC-like cells expressing CD11c, CD205, MHC II, and costimulatory molecules. Endogenous IL-13 was necessary to induce and sustain the increase in MHC II and CD40 expression by pulmonary CD11chigh cells, demonstrated by giving an IL-13 inhibitor as a measure of prevention or reversal to allergen-primed and -challenged mice. Conversely, IL-13 given by inhalation to naive mice increased the expression of MHC II and costimulatory molecules by CD11chigh cells in an IL-4Rα-dependent manner. We found that exogenous IL-13 exaggerated the immune and inflammatory responses to an inhaled, harmless Ag, whereas endogenous IL-13 was necessary for the priming of naive mice with an inhaled, harmless Ag. These data indicate that blockade of IL-13 may have therapeutic potential for controlling the immune response to inhaled Ags.

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Section: Discussionsupporting

confidence: 79%

IL-13 Regulates the Immune Response to Inhaled Antigens

Padilla

Daley

Chow

et al. 2005

The Journal of Immunology

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“…Both of these actions increase eosinophil survival. Second, IL-13 may play a unique role in the induction of the Th2 response by the skin route (37). Indeed, IL-13, more than IL-4, has been shown to be required for the priming of a Th2 response by soluble persistent Ags in the skin.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the 5q31-q33 Locus Shows an Association between IL13-1055C/T IL-13-591A/G Polymorphisms and Schistosoma haematobium Infections

Kouriba

Chevillard

Bream

et al. 2005

The Journal of Immunology

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Millions of humans are exposed to schistosome infections, which cause severe kidney and liver disease and 280,000 deaths annually. Th2-mediated immunity is critical to human defenses against this pathogen and susceptibility to infection is controlled by a major genetic locus that includes IL4, IL5, and IL13 genes. These observations led us to evaluate whether certain polymorphisms in IL4, IL5, or IL13 determine schistosome infection. The study was performed in two Dogon villages where Schistosoma haematobium is endemic. Schistosome infections were evaluated by counting eggs and measuring worm Ags in urine. Genetic polymorphisms were determined by restriction enzyme analysis or by primer extension and denaturing high-performance liquid chromatography analysis. Associations were tested using family-based association tests and logistical regression analysis. The alleles IL13-1055C (p = 0.05) and IL13-591A (p = 0.01) are shown, by family-based association test, to be preferentially transmitted to children with the 10% highest infections. A logistic regression analysis that included IL13-1055 G/G, G/T and T/T genotypes, age, gender, and village of residency, applied to the whole study population, showed that subjects bearing the IL13-1055T/T genotype were on average much less infected than individuals with other genotypes. Previous studies on asthma indicated that the IL13-1055T allele increased gene transcription, which is in agreement with the fact that this cytokine enhances resistance to infection by schistosome in humans.

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“…IL-13 was the major inducer of Th2 responses, being required independent of IL-4 (20). More recent studies have demonstrated that epicutaneous ovalbumin antigen exposure also induces IL-17, which drives the airway inflammation, even in the absence of IL-4 and IL-13 (21).…”

Section: Animal Models Of Chemical and Protein Allergen Skin Exposurementioning

confidence: 99%

“…Models of atopic asthma have likewise shown that epicutaneous allergen exposure with ovalbumin is highly effective at inducing Th2-like sensitization and subsequent lung asthmatic responses after ovalbumin airway challenge (20). IL-13 was the major inducer of Th2 responses, being required independent of IL-4 (20).…”

Section: Animal Models Of Chemical and Protein Allergen Skin Exposurementioning

confidence: 99%

Skin Exposure and Asthma: Is There a Connection?

Redlich¹

2010

Proceedings of the American Thoracic Society

100

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Numerous occupational and environmental exposures that increase asthma risk have been identified. Research and prevention have focused primarily on the respiratory tract. However, recent studies suggest that the skin may also be an important route of exposure and site of sensitization that contributes to asthma development. Factors that impair skin barrier function, such as filaggrin gene mutations or skin trauma, may facilitate allergen entry and promote Th2-like sensitization and subsequent asthma. Animal studies demonstrate that skin exposure to chemical and protein allergens is highly effective at inducing sensitization, with subsequent inhalation challenge eliciting asthmatic responses. A similar role for human skin exposure to certain sensitizing agents, such as isocyanates, is likely. Skin exposure methodologies are being developed to incorporate skin exposure assessment into epidemiology studies investigating asthma risk factors.Keywords: skin exposure; asthma; isocyanates; epidermal barrier function; sensitization Environmental and occupational asthma research and practice have focused primarily on the respiratory tract as the key route of exposure and pathogenesis. However, several lines of research support an important role for skin exposure in initiating and driving Th2-like immune responses and asthma. Human and animal studies of atopic dermatitis have identified skin epithelial barrier dysfunction, which may facilitate allergen entry, as a key factor in the development of atopic asthma and sensitization. This article highlights recent findings from a diverse literature that support the concept that skin may be an important site of exposure for certain occupational and environmental allergens.

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IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen

Cited by 92 publications

References 54 publications

IL-13 Regulates the Immune Response to Inhaled Antigens

IL-13 Regulates the Immune Response to Inhaled Antigens

Analysis of the 5q31-q33 Locus Shows an Association between IL13-1055C/T IL-13-591A/G Polymorphisms and Schistosoma haematobium Infections

Skin Exposure and Asthma: Is There a Connection?

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