IL-4-Dependent Th2 Collateral Priming to Inhaled Antigens Independent of Toll-Like Receptor 4 and Myeloid Differentiation Factor 88

Eisenbarth, Stephanie C.; Zhadkevich, Alex; Ranney, Patricia; Herrick, Christina A.; Bottomly, Kim

doi:10.4049/jimmunol.172.7.4527

Cited by 56 publications

(71 citation statements)

References 51 publications

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“…Interestingly, the lack of IL-12 production via limited TLR activation during the inflammatory/immune response appears to lead to Th2 responses, suggesting that this type of response is a default pathway that occurs in the absence of IL-12. Investigations have demonstrated that MyD88 knockout mice were not able to generate a Th1 response when challenged with an infectious agent (57)(58)(59)(63)(64)(65)(66). Also, MyD88-mediated cytokines appear to provide a suppressive signal for a Th2-type response.…”

Section: Notch Ligands Regulate Cytokine-dependent Responses and Partmentioning

confidence: 99%

“…The immune response is a highly regulated event involving a number of sophisticated and cross-regulated pathways shared by cellular players of the innate and acquired immune system (52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). Whereas the TLRs are known to be underpinnings of the innate immune response, they are also intimately involved in events that direct the adaptive immune response (49)(50)(51).…”

Section: Tlrs and The Adaptor Molecule Myeloid Differentiation Factormentioning

confidence: 99%

See 1 more Smart Citation

Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation

Raymond

Schaller²,

Hogaboam

et al. 2007

Proceedings of the American Thoracic Society

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Section: Notch Ligands Regulate Cytokine-dependent Responses and Partmentioning

confidence: 99%

Section: Tlrs and The Adaptor Molecule Myeloid Differentiation Factormentioning

confidence: 99%

Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation

Raymond

Schaller²,

Hogaboam

et al. 2007

Proceedings of the American Thoracic Society

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“…Recent studies demonstrated that a pre-existing Th immune response can modify the priming of naive Th cells toward new Ags (13,15). Additional experiments were designed to address the role of activated Th2 cells in the induction of Th2 phenotype spread observed in the above-described experimental asthma model.…”

Section: Activated Th2 Cells Are Sufficient For Induction Of Th2 Phenmentioning

confidence: 99%

“…Nevertheless, it is well established that IL-4, a Th2 cytokine, and IFN-␥, a Th1 cytokine, polarize naive CD4 ϩ T cells toward a Th2 and a Th1 phenotype, respectively, under in vitro conditions (11,12). Recent studies have demonstrated that a pre-existing memory-effector Th2 or Th1 immune response, via IL-4 or IFN-␥ secretion, respectively, affects Th polarization to a codelivered neo-Ag in vivo (13)(14)(15).…”

mentioning

confidence: 99%

Induction and Inhibition of the Th2 Phenotype Spread: Implications for Childhood Asthma

Hayashi

Gong

Rossetto

et al. 2005

The Journal of Immunology

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The interactions between genetic and environmental factors play a major role in the development of childhood asthma. We hypothesized that a pre-existing Th2/asthmatic response can promote Th2 responses to newly encountered Ags (i.e., phenotype spread). To test this hypothesis, we developed a mouse model in which the requirements for the induction and inhibition of phenotype spread to a clinically relevant neo-allergen (i.e., ragweed) were investigated. Our results indicate that 1) phenotype spread to the neo-allergen can be induced only within the first 8 h after a bronchial challenge with the first Ag (OVA); 2) Th2 differentiation of naive CD4+ T cells occurs in bronchial lymph nodes; 3) trafficking of naive CD4+ T cells to local lymph nodes and IL-4 produced by OVA-activated Th2 cells play essential roles in the differentiation of naive CD4+ T cells to Th2 cells; and 4) suppression of the production of chemokines involved in the homing of naive CD4+ T and Th2 cells to bronchial lymph nodes by a TLR9 agonist inhibited phenotype spread and abrogated the consequent development of experimental asthma. These findings provide a mechanistic insight into Th2 phenotype spread and offer an animal model for testing relevant immunomodulatory interventions.

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“…These studies demonstrated that immune-stimulating adjuvants like aluminum hydroxide (alum) are frequently required to elicit appropriate in vivo adaptive immunity. They also demonstrated that many of these adjuvants mediate their effects via activating innate immunity Toll-like receptors (TLRs) and NODs and inducing the production of proinflammatory cytokines (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). This can readily be appreciated in studies highlighting the important role(s) that TLRs plays in the pathogenesis of asthma-like Th2 adaptive immune responses (18) and studies that demonstrate that TLR-2 ligands such as Pam-3-cys are potent Th2 adjuvants in vivo (19,20).…”

mentioning

confidence: 99%

Chitin Particles Are Multifaceted Immune Adjuvants

Silva¹,

Pochard²,

Lee³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Chitin is a ubiquitous polysaccharide in fungi, insects, allergens, and parasites that is released at sites of infection. Its role in the generation of tissue inflammation, however, is not fully understood. Objectives: We hypothesized that chitin is an important adjuvant for adaptive immunity. Methods: Mice were injected with a solution of ovalbumin and chitin. Measurements and Main Results: We used in vivo and ex vivo/in vitro approaches to characterize the ability of chitin fragments to foster adaptive immune responses against ovalbumin and compared these responses to those induced by aluminum hydroxide (alum). In vivo, ovalbumin challenge caused an eosinophil-rich pulmonary inflammatory response, Th2 cytokine elaboration, IgE induction, and mucus metaplasia in mice that had been sensitized with ovalbumin plus chitin or ovalbumin plus alum. Toll-like receptor-2, MyD88, and IL-17A played critical roles in the chitin-induced responses, and MyD88 and IL-17A played critical roles in the alum-induced responses. In vitro, CD4 1 T cells from mice sensitized with ovalbumin plus chitin were incubated with ovalbumin-stimulated bone marrowderived dendritic cells. In these experiments, CD4 1 T-cell proliferation, IL-5, IL-13, IFN-g, and IL-17A production were appreciated. Tolllike receptor-2, MyD88, and IL-17A played critical roles in these in vitro adjuvant properties of chitin. TLR-2 was required for cell proliferation, whereas IL-17 and TLR-2 were required for cytokine elaboration. IL-17A also inhibited the generation of adaptive Th1 responses.Conclusions: These studies demonstrate that chitin is a potent multifaceted adjuvant that induces adaptive Th2, Th1, and Th17 immune responses. They also demonstrate that the adjuvant properties of chitin are mediated by a pathway(s) that involves and is regulated by TLR-2, MyD88, and IL-17A.

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IL-4-Dependent Th2 Collateral Priming to Inhaled Antigens Independent of Toll-Like Receptor 4 and Myeloid Differentiation Factor 88

Cited by 56 publications

References 51 publications

Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation

Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation

Induction and Inhibition of the Th2 Phenotype Spread: Implications for Childhood Asthma

Chitin Particles Are Multifaceted Immune Adjuvants

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