Selective Expression of a Stable Cell Surface Molecule on Type 2 but Not Type 1 Helper T Cells

Xu, Damo; Chan, Weng Onn; Leung, Bernard P.; Huang, Fang-Ping; Wheeler, Robert W.; Piedrafita, David; Robinson, John H.; Liew, F. Y.

doi:10.1084/jem.187.5.787

Cited by 482 publications

(445 citation statements)

References 36 publications

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“…Importantly, we found that naive CD4 1 T cells did not respond to IL-33 in the absence of DCs. This observation is consistent with the fact that naive T cells do not express ST2 and that IL-33 did not induce Th2 cytokines in non-polarized CD4 1 T cells [10,35,36]. The cytokine expression pattern of T cells polarized by IL-33-activated DCs differs from classical Th2 cells by the absence of IL-4 production.…”

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confidence: 87%

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

et al. 2011

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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...

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confidence: 87%

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

et al. 2011

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“…1 shows that IL-33 induced no reproducible effect on lymphocyte populations cultured overnight with medium alone (Fig. 1A), reflecting low levels of spontaneous expression of ST2 on the surface of resting T cells ( [2] and data not shown). In contrast, when CD4 + T cells from PBMC were activated overnight with platebound anti-CD3 antibody, phytohemagglutinin (PHA) or staphylococcal enterotoxin B (SEB), the cells polarized to IL-33 in a dose-dependent manner (Fig.…”

Section: Il-33 Induces Polarization and Migration Of Peripheral Bloodmentioning

confidence: 89%

“…Since we have previously shown that ST2 is preferentially expressed on activated Th2 cells [2], we next explored the hypothesis that IL-33 preferentially induced locomotion in Th2 cells. CD4 + T cells purified from PBMC were cultured under Th2 and Th1 differentiation conditions.…”

Section: Il-33 Induces Migration Of Th2 But Not Th1 Cellsmentioning

confidence: 99%

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IL‐33 is a chemoattractant for human Th2 cells

et al. 2007

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IL‐33 is a novel cytokine of the IL‐1 family and mediates its biological effect via the receptor ST2, which is selectively expressed on Th2 cells but not Th1 cells. IL‐33 drives production of Th2‐associated cytokines including IL‐5 and IL‐13 and thereby promotes defense and pathology in mucosal organs. Cell locomotion is crucial to the induction of an effective immune response. We report here the chemoattraction of Th2 cells by IL‐33. Recombinant IL‐33 increased the proportion of human Th2 cells, but not Th1 cells, in polarized morphology in vitro and stimulated their subsequent invasion into collagen gels in an IL‐33 concentration‐dependent manner. Injection of recombinant IL‐33 into the footpad of ST2–/– mice which had been adoptively transferred with polarized Th2 cells, led to local accumulation of the transferred Th2 cells. These data therefore demonstrate that IL‐33 is a selective Th2 chemoattractant associated with the pro‐inflammatory property of this novel cytokine.

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“…The expression of the three forms has been detected in various human tissues and cells, including hematopoietic and endothelial cells [25]. ST2L has been proposed as a marker for Th2 CD4+ T cells since it is selectively expressed on Th2 but not on Th1 CD4+ T cells [26,27] and might be involved in the effector phase of Th2 immune responses [28]. Expression of sST2 protein can be induced in vitro by pro-inflammatory stimuli, like lipo-polysaccaride (LPS), IL-1β, TNF-α and IL-6 in human and murine inflammatory models [25,29].…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of soluble ST2 protein in dengue virus infected patients

et al. 2008

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Levels of the soluble form of the interleukin-1 receptor like 1 protein (IL-1RL-1 / ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty four patients with confirmed dengue infection, classified as dengue fever, and eleven patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the febrile stage and at defervescence (p=0.0088 and p=0.0004 respectively). Patients with secondary dengue infections had higher serum sST2 levels compared with patients with primary dengue infections (p=0.047 at last day of fever and p=0.030 at defervescence). Furthermore, in dengue infected patients, we found a significant negative correlation of sST2 with platelet and WBC counts, and positive correlation with thrombin time and transaminases activity. We suggest that sST2 could be a potential marker of dengue infection, could be associated with severity or could play a role in the immune response in secondary dengue virus infection.

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Selective Expression of a Stable Cell Surface Molecule on Type 2 but Not Type 1 Helper T Cells

Cited by 482 publications

References 36 publications

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

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

IL‐33 is a chemoattractant for human Th2 cells

Elevated levels of soluble ST2 protein in dengue virus infected patients

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