Interleukin-1α controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33

Willart, Monique; Deswarte, Kim; Pouliot, Philippe; Braun, Harald; Beyaert, Rudi; Lambrecht, Bart N.; Hammad, Hamida

doi:10.1084/jem.20112691

Cited by 371 publications

(441 citation statements)

References 52 publications

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“…However, recapitulating our results from this study and the fact that functional IL-1R and IL-18R are expressed on B cells (54)(55)(56), IL-1a/b and IL-18 also stimulate B cells to promote GC responses and IgE/IgG1 production during the airway instillation of pollen allergens. The results demonstrated in this study are not contradictive to the roles for IL-1 family cytokines on epithelia, myeloid APCs, or T cells that were described previously (37)(38)(39)(40). B cellintrinsic MyD88 signaling may cooperatively activate Ab responses with MyD88 signaling in other cells, because the defective Ab responses were greater in systemic Myd88 2/2 mice than in B-Myd88 2/2 mice.…”

Section: Discussionsupporting

confidence: 71%

“…Furthermore, particles can induce cellular damage, resulting in the release of alarmins, including IL-1a (52). Although the involvement of IL-1 family cytokines in particulate matterinduced Th2 responses is controversial (26), IL-1 family cytokines might participate in IgE and IgG1 production in the lungs (37)(38)(39)(40)53).…”

Section: Discussionmentioning

confidence: 99%

“…IL-1R1-or IL-1a/b-deficient mice develop significantly reduced Th2 cell responses and IgE/IgG1 production in an OVA-induced asthma model (38,39). IL-1a is a critical mediator of house dust mice-induced pulmonary inflammation (40). Although the contribution of IL-1a/b and IL-18 in lung Th2 responses has been interpreted as an adjuvant effect through epithelial cells and APCs or a direct effect on CD4 + T cells, the role of these cytokines in B cells was previously unknown.…”

Section: Discussionmentioning

confidence: 99%

“…7). Thus, in addition to the effect of IL-1 family cytokines on epithelial cells, APCs, or T cells (37)(38)(39)(40), they stimulate B cells to fully activate the Ab responses in the lung Ag instillation model. Taken together, lung exposure of pollen allergens induces the production of IL-1a/b and IL-18, which, in turn, activate B cell-intrinsic MyD88 signaling to facilitate Ab production.…”

Section: B Cell-intrinsicmentioning

confidence: 99%

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B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

Matsushita

Yoshimoto

2014

The Journal of Immunology

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Allergen-specific IgE is linked to asthma pathogenesis, but the underlying mechanisms of IgE production in response to allergen exposure are poorly understood. In this article, we show that B cell–intrinsic MyD88 is essential for IgE/IgG1 production evoked by ragweed pollen instilled into lungs. MyD88-deficient mice showed defective IgE/IgG1 production and germinal center responses to lung instillation of ragweed pollen. However, MyD88 was dispensable for dendritic cell activation and Th2 cell development. B cell–specific deletion of MyD88 replicated the defective Ab production observed in MyD88-deficient mice. Although ragweed pollen contains TLR ligands, TLR2/4/9-deficient mice developed normal allergic responses to ragweed pollen. However, anti–IL-1R1 Ab-treated mice and IL-18–deficient mice showed decreased IgE/IgG1 production with normal Th2 development. Furthermore, B cell–specific MyD88-deficient mice showed reduced IgE/IgG1 production in response to lung instillation of OVA together with IL-1α, IL-1β, or IL-18. Thus, pollen instillation into lungs induces IL-1α/β and IL-18 production, which activates B cell–intrinsic MyD88 signaling to promote germinal center responses and IgE/IgG1 production.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: B Cell-intrinsicmentioning

confidence: 99%

See 2 more Smart Citations

B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

Matsushita

Yoshimoto

2014

The Journal of Immunology

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“…3B). It is therefore conceivable that ILC2 may act in parallel with epithelial cells that are induced by HDM to produce CCL20 and GM-CSF to support recruitment and activation of DCs (46). Further experiments should identify chemokines and cytokines that are produced by activated ILC2.…”

Section: Discussionmentioning

confidence: 99%

Enforced Expression of Gata3 in T Cells and Group 2 Innate Lymphoid Cells Increases Susceptibility to Allergic Airway Inflammation in Mice

KleinJan

Wolterink

Levani

et al. 2014

The Journal of Immunology

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Airway inflammation in allergic asthma reflects a threshold response of the innate immune system, including group 2 innate lymphoid cells (ILC2), followed by an adaptive Th2 cell–mediated response. Transcription factor Gata3 is essential for differentiation of both Th2 cells and ILC2. We investigated the effects of enforced Gata3 expression in T cells and ILC2 on the susceptibility of mice to allergic airway inflammation (AAI). We used CD2-Gata3 transgenic (Tg) mice with enforced Gata3 expression driven by the CD2 promoter, which is active both in T cells and during ILC2 development. CD2-Gata3 Tg mice and wild-type (WT) littermates were analyzed in mild models of AAI without adjuvants. Whereas OVA allergen exposure did not induce inflammation in WT controls, CD2-Gata3 Tg mice showed clear AAI and enhanced levels of IL-5 and IL-13 in bronchoalveolar lavage. Likewise, in house dust mite–driven asthma, CD2-Gata3 Tg mice were significantly more susceptible to AAI than WT littermates, whereby both ILC2 and Th2 cells were important cellular sources of IL-5 and IL-13 in bronchoalveolar lavage and lung tissue. Compared with WT littermates, CD2-Gata3 Tg mice contained increased numbers of ILC2, which expressed high levels of IL-33R and contributed significantly to early production of IL-4, IL-5, and IL-13. CD2-Gata3 Tg mice also had a unique population of IL-33–responsive non-B/non-T lymphoid cells expressing IFN-γ. Enforced Gata3 expression is therefore sufficient to enhance Th2 and ILC2 activity, and leads to increased susceptibility to AAI after mild exposure to inhaled harmless Ags that otherwise induce Ag tolerance.

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Dendritic Cells in Inflammatory Disease

Lambrecht

Guilliams

Hammad

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

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Interleukin-1α controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33

Abstract: IL-1α promotes a cascade of cytokine production from epithelial cells culminating in Th2 immunity to house dust mite allergens.

Cited by 371 publications

References 52 publications

B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

Enforced Expression of Gata3 in T Cells and Group 2 Innate Lymphoid Cells Increases Susceptibility to Allergic Airway Inflammation in Mice

Dendritic Cells in Inflammatory Disease

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