CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation

Allakhverdi, Zoulfia; Comeau, Michael R.; Smith, Dirk E.; Toy, Dean; Endam, Léandra Mfuna; Desrosiers, Martin; Liu, Yongjun; Howie, Karen; Denburg, Judah A.; Gauvreau, Gail M.; Delespesse, Guy

doi:10.1016/j.jaci.2008.10.022

Cited by 215 publications

(197 citation statements)

References 30 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…It can be concluded that IL-33 is capable of inducing the expansion of a subpopulation of CD117 + granulocyte/monocyte progenitors that were characterized by their dependency on IL-5 (44); however, it is not clear whether this is achieved in a direct or indirect fashion. Our finding is consistent with a recent study demonstrating that human hematopoietic CD34 + cells from asthma patients express ST2L and produce IL-5 in response to IL-33 (45). Thus, IL-33-driven eosinophilia is likely, at least in part, a consequence of IL-5 produced by IL-33-induced CD117 + hematopoietic precursors in the bone marrow compartment in an autocrine manner.…”

Section: Discussionsupporting

confidence: 93%

IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation

Stolarski

Kurowska‐Stolarska

Kewin

et al. 2010

The Journal of Immunology

260

206

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation

Stolarski

Kurowska‐Stolarska

Kewin

et al. 2010

The Journal of Immunology

260

206

View full text Add to dashboard Cite

show abstract

“…In vitro, we observed that IL-33 potently activates BMDCs to produce proinflammatory cytokines IL-6, TNF, IL-1b and the chemokine CCL17, but not IL-12p40 or IL-23p19 (data not shown). IL-6 and CCL17 production by DCs was related to T cell differentiation into Th2 type [7,31,32]. We also found that IL-33 treatment upregulates cell surface expression of CD40, CD80 and OX40L on DCs.…”

Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

“…Th2 cells have been shown to play a predominant role in allergic asthma and Th2 cytokines, such as IL-4, IL-5 and IL-13, exacerbate disease severity [3,4]. IL-33, the recently discovered Th2 cytokine, is found at high levels in the plasma of asthmatic patients [5,6] and in the lungs of mice during experimental allergic asthma [7,8].IL-33 is a member of IL-1 family [9][10][11]. Like IL-1b or IL-18, IL-33 is synthesized as a precursor and can be cleaved by caspase-1 and 3 but the cleavage products are biologically less active than the precursor [12,13].…”

mentioning

confidence: 99%

See 1 more Smart Citation

IL‐33‐activated dendritic cells are critical for allergic airway inflammation

et al. 2011

View full text Add to dashboard Cite

IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1b, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation. IntroductionAllergic asthma is a chronic disorder characterized by eosinophilic airway inflammation, mucus hypersecretion, antigenspecific-IgE antibodies, airway remodeling and increased airway hyperreactivity [1,2]. The process of airway inflammation involves various cells types, such as eosinophils, mast cells, epithelial cells, lymphocytes and DCs. Th2 cells have been shown to play a predominant role in allergic asthma and Th2 cytokines, such as IL-4, IL-5 and IL-13, exacerbate disease severity [3,4]. IL-33, the recently discovered Th2 cytokine, is found at high levels in the plasma of asthmatic patients [5,6] and in the lungs of mice during experimental allergic asthma [7,8].IL-33 is a member of IL-1 family [9][10][11]. Like IL-1b or IL-18, IL-33 is synthesized as a precursor and can be cleaved by caspase-1 and 3 but the cleavage products are biologically less active than the precursor [12,13]. In contrast to the other IL-1 family members, IL-33 is mainly expressed in non-hematopoietic cells such as fibroblasts, epithelial cells and endothelial cells [10,14,15]. Because of its nuclear localization sequence, IL-33 is usually present in the nucleus, where it acts as a potential transcriptional repressor [16]. Recently, IL-33 has been shown to be released from necrotic cells and may act as an alarmin in a similar manner to IL-1a [17] or high mobility group box1 protein HMGB1 [18,19]. [14]. In accordance with its Th2 functions, administration of IL-33 into naive mice induces severe inflammation in the lung and digestive tract with elevated levels of IL-4, IL-5 and IL-13, splenomegaly and increased serum Ig [10]. In vitro, IL-33 has also been reported to polarize naive CD4 1 T cells to produce IL-5 and IL-13, but not . Polarization of this atypical Th2 population is independent of IL-4, STAT6 and GATA3. On macrophages, IL-33 amplifies IL-13-mediated polarization...

show abstract

“…These cells produce inflammatory cytokines and chemokines, including IL-4, IL-5, IL-6, IL-13, and IL-8, by stimulation of IL-33 (5,7,9,30). Recently, it has been reported that circulating CD34 ϩ hematopoietic progenitors expressed ST2 and responded to IL-33 by releasing high levels of Th2-associated cytokines (31). Such results suggest potential roles of IL-33 in Th2-associated immune responses, and IL-33 seems to be closely related to allergic inflammatory diseases, including asthma and atopic dermatitis.…”

mentioning

confidence: 99%