IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response

Nakae, Susumu; Komiyama, Yutaka; Yokoyama, Hiroshi; Nambu, Aya; Umeda, Masaomi; Iwase, Michiko; Homma, Ikuo; Sudo, Katsuko; Horai, Reiko; Asano, Masahide; Iwakura, Yoichiro

doi:10.1093/intimm/dxg054

Cited by 133 publications

(105 citation statements)

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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-1a and IL-1b might also participate in the pathogenesis of lung allergic diseases. 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).…”

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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“…Additionally, in this latter study, IL-1␣␤ Ϫ/Ϫ mice exhibited defective IgM and IgG anti-TNP responses to the TI-2 Ag, TNPFicoll, but normal responses to the TI-1 Ag, TNP-LPS. Finally, IL-1 ␣␤ Ϫ/Ϫ mice exhibited decreased serum titers of OVAspecific IgG1 and IgE in a Th2 OVA-induced model of airway hypersensitivity (14).…”

Section: Discussionmentioning

confidence: 92%

Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to IntactStreptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine

Chen

Sen

Snapper

2006

The Journal of Immunology

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MyD88−/− mice exhibit defective innate, diminished CD4+ T cell-dependent (TD) type 1, but enhanced type 2, humoral immunity in response to intact Streptococcus pneumoniae (Pn). Because type 1 IL-1R (IL-1R1) signaling is MyD88 dependent, a role for endogenous IL-1 was determined. IL-1R1−/−, in contrast to MyD88−/−, mice exhibited relatively intact innate splenic cytokine expression in response to Pn. Nevertheless, IL-1R1−/−, like MyD88−/−, mice were more sensitive to killing with live Pn relative to wild-type controls. Although IL-1R1−/− mice elicited a normal T cell-independent IgM antipolysaccharide (PS) response to heat-killed Pn, the induction of PS- and protein-specific cognate, but not noncognate, TD type 1 and type 2 IgG isotypes were markedly reduced. Additionally, CD4+ T cells from Pn-primed IL-1R1−/− mice failed to elicit IFN-γ, IL-5, or IL-13 secretion upon restimulation with Pn in vitro, whereas MyD88−/− mice secreted normal levels of IFN-γ and enhanced levels of IL-5 and IL-13. In contrast, IgG responses to a soluble, pneumococcal protein-PS conjugate, with or without adjuvant, showed little dependence on IL-1R1 and normal CD4+ T cell priming. These data are the first to demonstrate a nonredundant role for endogenous IL-1 in TD induction of humoral immune responses to an intact pathogen, although not a pathogen-derived soluble conjugate, suggesting that antigenic context is a key determinant for IL-1 dependence. These data further suggest that IL-1 may be critical for preserving CD4+ Th2 function in the presence, but not absence, of MyD88-dependent signaling via TLRs.

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IL‐1‐dependent, IL‐1R1‐independent resistance to gastrointestinal nematodes

Humphreys

Grencis

2009

Eur J Immunol

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IL-1 null mice are unable to expel the intestinal nematode Trichuris muris; whereas WT littermates exhibit sterile immunity. Intriguingly the essential signalling components IL-1R1 and IL-1R accessory protein (AcP) are dispensable for expulsion of this parasite. IL-1 is thus critical for CD41 Th2-mediated immunity to T. muris; however, this action is independent of the established IL-1 signalling receptor. We also present data demonstrating that both IL-1a and IL-1b induce measurable effects on T. muris primed cells isolated from IL-1R1 or IL-1R AcP null mice. MLN cells from these mice restimulated with parasite antigen proliferated at a greater rate and produced more cytokines in response to exogenous IL-1. This ability to respond to IL-1 was restricted to these parasite-primed cells and importantly was not evident in cells from naïve gene null mice. These in vitro data are consistent with the observed ability of mice with compromised IL-1 signalling to expel the parasite, bolstering the premise that an alternative IL-1 signalling mechanism is accessible in the context of an intestinal helminth-driven Th2 immune response.Key words: Cytokine . Infection . Parasitic-helminth . Proinflammatory . T cells IntroductionIL-1 is a potent molecule; indeed when unregulated the resultant inflammatory cytokine cascade has profound pathological effects [1,2]. Thus by necessity IL-1 bioactivity is tightly controlled, requiring both posttranslational processing and a signalling receptor containing IL-1R1 and IL-1R accessory protein (AcP). This pathway to IL-1 action is policed by a decoy receptor IL-1R2, a natural sink for IL-1 [3] and IL-1RA, which competitively binds IL-1R1, preventing IL-1RAcP recruitment and signal transduction [4]. Importantly, IL-1RA only weakly interacts with IL-1R2, thus preventing the inhibition of the inhibitor [5]. This pleiotropic cytokine plays critical roles in a variety of inflammatory and non-inflammatory diseases. Pathological functions have been demonstrated in rheumatoid arthritis [6][7][8], Alzheimer's disease [9], multiple myeloma [10] and leukaemia [11][12][13]. Importantly for this study the involvement of IL-1 in the inflamed intestinal mucosa is also well established. Patients with ulcerative colitis significantly over express , with the principle sources identified as colon subepithelial macrophages [19,20], follicular epithelial M cells [21] and lamina propria T cells [22]. IL-1 also influences adaptive immunity, altering the CD4 1 Th-cell balance, though published data demonstrate contradictory changes in both Th1 and Th2 immune polarisation [23][24][25][26][27][28]. For example, IL-1a/b null mice show reduced Th2 responses to ovalbumin-induced airway hypersensitivity [29,30], whereas conversely, IL-1a has been shown to enhance Th1-driven immunity to Leishmania major in BALB/c mice [31]. Thus understanding the interplay of IL-1 and T-cell polarisation is complex and highly dependent on model, strain of mouse and method of IL-1 manipulation. Here, to better understand this role of IL...

show abstract

IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response

Cited by 133 publications

References 38 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

Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to IntactStreptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine

IL‐1‐dependent, IL‐1R1‐independent resistance to gastrointestinal nematodes

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