Developmental changes in interleukin‐12‐producing ability by monocytes and their relevance to allergic diseases

Itazawa, Toshiko; Okabe, Yasunori; Hamamichi, Miki; Adachi, Y; Toyoda, Masahiko; Morohashi, Masaaki; Miyawaki, T

doi:10.1046/j.1365-2222.2003.01608.x

Cited by 20 publications

(14 citation statements)

References 19 publications

(23 reference statements)

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“…Understanding the molecular pathway that drives Th2 polarization and in turn induces allergen-specific IgE production in individuals with AD is critical to the further development of therapeutic approaches for AD and potentially for atopic disease in general. Some previous studies have shown deficient Th1 pathways in circulating antigen-presenting cells/monocytes (IL-12) in AD, but others have shown opposing results (Itazawa et al, 2003;Piancatelli et al, 2008). We therefore set out to explore the immunological outcome of the same antigenic stimulus in the skin of individuals with AD versus non-atopic controls.…”

Section: Or (B) Ifn-g Production By Peripheral Blood Mononuclear Cellmentioning

confidence: 99%

Sensitization via Healthy Skin Programs Th2 Responses in Individuals with Atopic Dermatitis

Newell

Polak

Perera

et al. 2013

Journal of Investigative Dermatology

113

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Allergen-specific responses in atopic dermatitis (AD) are skewed toward a Th2 profile. However, individuals with AD have been shown to make effective virus-specific Th1 responses, raising the possibility that the skin itself contributes to driving the AD Th2 immunophenotype. Therefore, to explore the programming of immunological sensitization by the skin, we examined the outcome of sensitization through non-lesional skin of individuals with AD and healthy controls. Volunteers (controls, AD individuals with filaggrin gene (FLG) mutations (ADFM), and AD individuals without FLG mutations (ADWT)) were sensitized by cutaneous application of 2,4-dinitrochlorobenzene (DNCB), a small, highly lipophilic chemical sensitizer. At the doses tested, DNCB showed equal penetration into skin of all groups. Clinical reactions to DNCB were significantly reduced in AD. Although both controls and AD made systemic DNCB-specific Th1 responses, these were reduced in AD and associated with significantly Th2-skewed DNCB-specific T-cell responses. Th2 skewing was seen in both ADFM and ADWT, with no difference between these groups. After 3 months, DNCB-specific Th2 responses were persistent in individuals with AD, and Th1 responses persisted in controls. These data provide evidence that when antigen penetration is not limiting, AD skin has a specific propensity to Th2 programming, suggesting the existence of altered skin immune signaling that is AD-specific and independent of FLG status.

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Section: Or (B) Ifn-g Production By Peripheral Blood Mononuclear Cellmentioning

confidence: 99%

Sensitization via Healthy Skin Programs Th2 Responses in Individuals with Atopic Dermatitis

Newell

Polak

Perera

et al. 2013

Journal of Investigative Dermatology

113

View full text Add to dashboard Cite

show abstract

“…Recently, it has become clear that the differentiation of naïve helper lymphocyte (Th0) into Th1 or Th2 effectors is determined or at least affected by the following factors: soluble factors [IL-12 versus IL-4, IL-12 versus prostaglandin E 2 ], the nature and strength of the T cell receptor-mediated signal, and the nature, strength and/or timing of the co-stimulatory signals endowed by antigen 0165 presenting cells. A reduced ability to produce IL-12, which is a key cytokine for the induction of Th1 responses, has been proposed to lead to aberrant Th2 development in these disease conditions [8]. These findings suggest that cigarette smoke contains substances that may alter the Th1/Th2 balance via down-regulation of IL-12.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of interleukin-12 production in mouse macrophages by hydroquinone, a reactive metabolite of benzene, via suppression of nuclear factor-κB binding activity

2005

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“…First, DCs from atopic individuals and their immediate blood monocyte precursors produce less IL-12p70 compared with nonatopic controls [19,20]. Second, sensitization to inhaled aller-gens occurs predominantly before the age of 12, when the capacity to produce IL-12 is severely reduced compared with adults, potentially explaining the Th2 bias at a young age [21,22]. In children at risk for allergic diseases, low IL-12 production by circulating DCs in the neonatal period is associated with stronger Th2 responses to inhaled and food allergens [23].…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization

Kuipers

Heirman

Hijdra

et al. 2004

Journal of Leukocyte Biology

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It has been postulated that low-level interleukin (IL)-12 production of antigen-presenting cells is associated with the risk of developing atopic asthma. To study the relationship between IL-12 production capacity of dendritic cells (DCs) and development of T helper type 2 (Th2) responses in the lung, we genetically engineered DCs to constutively overexpress bioactive IL-12. Retrovirally mediated overexpression of IL-12 in DCs strongly polarized naive ovalbumin (OVA)-specific CD4+ T cells toward Th1 effector cells in vitro. After intratracheal injection, OVA-pulsed IL-12-overexpressing DCs failed to induce Th2 responses in vivo and no longer primed mice for Th2-dependent eosinophilic airway inflammation upon OVA aerosol challenge, readily observed in mice immunized with sham-transfected, OVA-pulsed DCs. Analysis of a panel of cytokines and chemokines in the lung demonstrated that the lack of Th2 sensitization was accompanied by increased production of the Th1 cytokine interferon-gamma (IFN-gamma), chemokines induced by IFN-gamma, and the immunoregulatory cytokine IL-10. When Th2 priming was induced using OVA/alum prior to intratracheal DC administration, DCs constitutively expressing IL-12 were no longer capable of preventing eosinophilic airway inflammation and even enhanced it. These data show directly that high-level expression of IL-12 in DCs prevents the development of Th2 sensitization. Enhancing IL-12 production in DCs should be seen as a primary prevention strategy for atopic disorders. Enhancing IL-12 production in DCs is less likely to be of benefit in already Th2-sensitized individuals.

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Developmental changes in interleukin‐12‐producing ability by monocytes and their relevance to allergic diseases

Abstract: IL-12 appeared to play different roles in the pathogenesis of allergic diseases between younger and older ages.

Cited by 20 publications

References 19 publications

Sensitization via Healthy Skin Programs Th2 Responses in Individuals with Atopic Dermatitis

Sensitization via Healthy Skin Programs Th2 Responses in Individuals with Atopic Dermatitis

Inhibition of interleukin-12 production in mouse macrophages by hydroquinone, a reactive metabolite of benzene, via suppression of nuclear factor-κB binding activity

Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization

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