Activated, but not resting human Th2 cells, in contrast to Th1 and T regulatory cells, produce soluble ST2 and express low levels of ST2L at the cell surface

Lécart, Sandrine; Lecointe, Nathalie; Subramaniam, Arun; Alkan, Şefik Ş.; Ni, Donghui; Chen, Rong; Boulay, Véra; Pène, Jérôme; Kuroiwa, Kenji; Tominaga, Shin‐ichi; Yssel, Hans

doi:10.1002/1521-4141(2002010)32:10<2979::aid-immu2979>3.0.co;2-5

Cited by 70 publications

(49 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, ST2 is inducible in human Th2 cells, and human Th2 cells express ST2 on their cell surface and secrete ST2 following activation. 9 Several lines of evidence suggest that the ST2 expressed on Th2 cells 8 and mast cells 10 is linked to important Th2 effector functions. 8 Exogenous administration of soluble ST2 has been demonstrated to effectively neutralize the putative ligand, resulting in alleviation of inflammation by abrogating Th2 cytokine production and induction of the eosinophilic inflammatory response.…”

supporting

confidence: 89%

Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils

Suzukawa

Koketsu

Iikura

et al. 2008

Laboratory Investigation

186

154

View full text Add to dashboard Cite

Eosinophils are important effector cells in allergic diseases, but the mechanisms regulating their biological functions remain obscure. Interleukin-33 (IL-33) is a recently identified cytokine of the IL-1 family, and it reportedly accelerates the production of Th2-associated cytokines and promotes tissue inflammation. However, the action of IL-33 on effector cells such as eosinophils has remained unclear. In this study, we investigated the effects of IL-33 on eosinophil activation, assessed in terms of the cells' adhesiveness, expression of CD11b and apoptosis. Adhesiveness was quantified by measuring eosinophil peroxidase content of adherent eosinophils, and expression of CD11b was measured by flow cytometry. Apoptosis was determined by flow cytometry based on the ability of cells to bind annexin V. Real-time PCR analysis showed that eosinophils expressed mRNA for ST2, a putative receptor for IL-33. IL-33 at 1-100 ng/ml enhanced the adhesiveness and CD11b expression of eosinophils even more potently than IL-5. IL-33 maintained the viability of eosinophils. Treatment with neutralizing antibodies to ST2 eliminated the effects of IL-33 on eosinophil CD11b expression and cell survival. However, IL-33 did not elicit degranulation or leukotriene C4 synthesis in eosinophils. These findings indicate that IL-33 potently induces eosinophil adhesion and CD11b expression and enhances eosinophil survival. The IL-33-ST2 pathway might be an important regulator of eosinophil biology in the pathogenesis of Th2-biased allergic diseases.

show abstract

supporting

confidence: 89%

Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils

Suzukawa

Koketsu

Iikura

et al. 2008

Laboratory Investigation

186

154

View full text Add to dashboard Cite

show abstract

“…Total RNA was extracted from human colonic biopsies, mouse ilea, freshly isolated IEC and HT-29 cells and RT-PCR was performed by using specific primers, as described (38)(39)(40)(41). For full description, see SI Materials and Methods.…”

Section: Ihcmentioning

confidence: 99%

Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis

Pastorelli

Garg

Hoang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

366

395

View full text Add to dashboard Cite

IL-33 is a novel member of the IL-1 family and ligand for the IL-1 receptor-related protein, ST2. Recent evidence suggests that the IL-33/ST2 axis plays a critical role in several autoimmune and inflammatory disorders; however, its role in inflammatory bowel disease (IBD) has not been clearly defined. We characterized IL-33 and ST2 expression and modulation after conventional anti-TNF therapy in Crohn's disease and ulcerative colitis (UC) patients and investigated the role of IL-33 in SAMP1/YitFc (SAMP) mice, a mixed Th1/Th2 model of IBD. Our results showed a specific increase of mucosal IL-33 in active UC, localized primarily to intestinal epithelial cells (IEC) and colonic inflammatory infiltrates. Importantly, increased expression of full-length IL-33, representing the most bioactive form, was detected in UC epithelium, whereas elevated levels of cleaved IL-33 were present in IBD serum. ST2 isoforms were differentially modulated in UC epithelium, and sST2, a soluble decoy receptor with anti-inflammatory properties, was also elevated in IBD serum. Infliximab (anti-TNF) treatment of UC decreased circulating IL-33 and increased sST2, whereas stimulation of HT-29 IEC confirmed IL-33 and sST2 regulation by TNF. Similarly, IL-33 significantly increased and correlated with disease severity, and potently induced IL-5, IL-6, and IL-17 from mucosal immune cells in SAMP mice. Taken together, the IL-33/ST2 system plays an important role in IBD and experimental colitis, is modulated by anti-TNF therapy, and may represent a specific biomarker for active UC.inflammatory bowel disease | anti-TNF therapy | SAMP1/YitFc mouse model

show abstract

“…The involvement of sST2 has been observed in a variety of pathological conditions characterized by: (1) intravascular inflammation [145,[148][149][150][151] (i.e. myocardial infarction [152][153][154], atherosclerotic vascular disease [155], sepsis and trauma [149,150]); and (2) an imbalance of Th1/Th2 immune response [141,156,157] (i.e. asthma and other allergic conditions [145,148,158,159]), both of which are also observed in patients with preeclampsia [23,25,132,160,161].…”

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis. Methods: This cross-sectional study included women with preeclampsia (n ¼ 106) and women with an uncomplicated pregnancy (n ¼ 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte. Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p50.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p ¼ 0.7 and p ¼ 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho ¼ 0.72 and 0.63; each p50.0001), and negatively with PlGF (Spearman's Rho ¼ À0.56, p50.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (537 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors. Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the uteroplacental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic f...

show abstract

Activated, but not resting human Th2 cells, in contrast to Th1 and T regulatory cells, produce soluble ST2 and express low levels of ST2L at the cell surface

Cited by 70 publications

References 40 publications

Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils

Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils

Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Contact Info

Product

Resources

About