Role of the β Common (βc) Family of Cytokines in Health and Disease

Hercus, Timothy R.; Kan, Winnie L.; Broughton, Sophie E.; Tvorogov, Denis; Ramshaw, Hayley S.; Sandow, Jarrod J.; Nero, Tracy L.; Dhagat, Urmi; Thompson, Emma J.; Shing, Karen S. Cheung Tung; McKenzie, Duncan R.; Wilson, Nicholas J.; Owczarek, Catherine M.; Vairo, Gino; Nash, Andrew D.; Tergaonkar, Vinay; Hughes, Timothy P.; Ekert, Paul G.; Samuel, Michael S.; Bonder, Claudine S.; Grimbaldeston, Michele A.; Parker, Michael W.; Lopez, Angel F.

doi:10.1101/cshperspect.a028514

Cited by 35 publications

(46 citation statements)

References 211 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43,44 Upon entry into circulation, eosinophils have a short half-life before distribution into diverse tissue sites, including the lung. 11 Understanding whether variability patterns are due to different mechanisms would have important clinical implications. Our data suggest heterogeneity in blood eosinophil variability and thus raise the question of whether variability is due to differences in underlying mechanisms particularly since cytokines in addition to IL-5 can stimulate eosinophil production and function.…”

Section: Discussionmentioning

confidence: 99%

“…Our data suggest heterogeneity in blood eosinophil variability and thus raise the question of whether variability is due to differences in underlying mechanisms particularly since cytokines in addition to IL-5 can stimulate eosinophil production and function. 11 Understanding whether variability patterns are due to different mechanisms would have important clinical implications.…”

Section: Discussionmentioning

confidence: 99%

“…11 The development of agents that target IL-5 for treatment of asthma makes it imperative that clinicians have tools to identify patients with eosinophilic characteristics. 11 The development of agents that target IL-5 for treatment of asthma makes it imperative that clinicians have tools to identify patients with eosinophilic characteristics.…”

mentioning

confidence: 99%

“…airway, survival, and activation. 11 The development of agents that target IL-5 for treatment of asthma makes it imperative that clinicians have tools to identify patients with eosinophilic characteristics.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Variability of blood eosinophils in patients in a clinic for severe asthma

Rakowski

Zhao

Liu

et al. 2019

Clin Experimental Allergy

View full text Add to dashboard Cite

Background: Blood eosinophils are used to determine eligibility for agents targeting IL-5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation.Objective: To characterize variability and patterns of variability of blood eosinophil levels in a real-world clinic for severe asthmatics.Methods: Retrospective review of blood eosinophils measured over a 5-year period in patients enrolled in an urban clinic. Repeated measures of blood eosinophil levels in individuals were evaluated, and cluster analysis was performed to characterize patients by eosinophil patterns. Clinical characteristics associated with eosinophil levels and patterns of variability were analysed. Results:Patients treated in the Bellevue Hospital Asthma Clinic within a 3-month period were identified (n = 219). Blood eosinophil measures were obtained over the previous 5 years. Only 6% (n = 13) of patients had levels that were consistently above 300 cells/μL. Nearly 50% (n = 104) had eosinophil levels that traversed the threshold of 300 cells/μL. In contrast, 102 (46%) had levels that never reached the threshold of 300 cells/μL. Cluster analyses revealed three clusters with differing patterns of levels and variability. There was a suggestion of decreased clinical control and increased atopy in the cluster with the greatest variability in blood eosinophil measures. Conclusion:In an urban clinic for patients referred for uncontrolled asthma, blood measures of eosinophils were variable and showed differing patterns of variability.These data reinforce the need to perform repeated eosinophil blood measures for appropriate designation for therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Variability of blood eosinophils in patients in a clinic for severe asthma

Rakowski

Zhao

Liu

et al. 2019

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…M07e is a cytokine dependent cell line (16) that is generally cultured in the presence of Granulocyte-macrophage colony-stimulating factor (GM-CSF). The finding that KIT and PDGFRA expressions are required under GM-CSF stimulation raised the possibility that GM-CSF receptor activity could be dependent on KIT and PDGFRA.…”

mentioning

confidence: 99%

Screening of clustered regulatory elements reveals functional cooperating dependencies in Leukemia

Benbarche

Lopez

Salataj

et al. 2019

Preprint

View full text Add to dashboard Cite

In the recent years, massively parallel sequencing approaches identified hundreds of mutated genes in cancer(1) providing an unprecedented amount of information about mechanisms of cancer cell maintenance and progression. However, while (it is widely accepted that) transformation processes result from oncogenic cooperation between deregulated genes and pathways, the functional characterization of candidate key players is mostly performed at the single gene level which is generally inadequate to identify these oncogene circuitries. In addition, studies aimed at depicting oncogenic cooperation involve the generation of challenging mouse models or the deployment of tedious screening pipelines. Genome wide mapping of epigenomic modifications on histone tails or binding of factors such as MED1 and BRD4 allowed identification of clusters of regulatory elements, also termed Super-Enhancers (SE)(2). Functional annotation of these regions revealed their high relevance during normal tissue development and cancer ontogeny(3). An interesting paradigm of the tumorigenic function of these SE regions comes from ETO2-GLIS2-driven acute megakaryoblastic leukemia (AMKL) in which the fusion protein ETO2-GLIS2 is sufficient to promote an aberrant transcriptional network by the rewiring of SE regions(4). We thus hypothesized that important regulatory regions could control simultaneously expression of genes cooperating in functional modules to promote cancer development. In an effort to identify such modules, we deployed a genome-wide CRISPRi-based screening approach and nominated SE regions that are functionally linked to leukemia maintenance. In particular, we pinpointed a novel SE region regulating the expression of both tyrosine kinases KIT and PDGFRA. Whereas the inhibition of each kinase alone affected modestly cancer cell growth, combined inhibition of both receptors synergizes to impair leukemia cell growth and survival. Our results demonstrate that genome-wide screening of regulatory DNA elements can identify co-regulated genes collaborating to promote cancer and could open new avenues to the concept of combined gene inhibition upon single hit targeting.Super-Enhancers (SE) are clusters of regulatory elements characterized by high intensity of enhancer-related histone tail modifications such as histone H3 lysin 27 acetylation or lysine 4 mono-methylation (H3K27ac and H3K4me1 respectively) and binding of enhancerassociated factors such as the mediator complex, in particular MED1, or bromodomaincontaining proteins such as BRD4(5). These clustered regulatory regions shape the transcriptional identity of specific tissues and cell types and their landscape often shifts in disease conditions particularly in cancer cells where they can control oncogene expression (6, 7). Whether these regions control expression of one or several genes and what are the genes directly controlled by these regions is mainly unknown. Additionally, whether these regions contribute to transformation or disease progression remains to be characterized. We hy...

show abstract

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate

Najafi

Ghanavat

Shahrabi

et al. 2021

Cell Biology International

View full text Add to dashboard Cite

Inflammatory cytokines exert different effects on hematopoietic stem cells (HSCs), lead to the development of various cell lineages in bone marrow (BM) and are thus a differentiation axis for HSCs. The content used in this article has been obtained by searching PubMed database and Google Scholar search engine of English‐language articles (1995–2020) using “Hematopoietic stem cell,” “Inflammatory cytokine,” “Homeostasis,” and “Myelopoiesis.” Inflammatory cytokines are involved in the differentiation and proliferation of hematopoietic progenitors to compensate for cellular death due to inflammation. Since each of these cytokines differentiates HSCs into a specific cell line, the difference in the effect of these cytokines on the fate of HSC progenitors can be predicted. Inhibitors of these cytokines can also control the inflammatory process as well as the cells involved in leukemic conditions. In general, inflammatory signaling can specify the dominant cell line in BM to counteract inflammation and leukemic condition via stimulating or inhibiting hematopoietic progenitors. Therefore, detection of the effects of inflammatory cytokines on the differentiation of HSCs can be an appropriate approach to check inflammatory and leukemic conditions and the suppression of these cytokines by their inhibitors allows for control of homeostasis in stressful conditions.

show abstract

Role of the β Common (βc) Family of Cytokines in Health and Disease

Cited by 35 publications

References 211 publications

Variability of blood eosinophils in patients in a clinic for severe asthma

Variability of blood eosinophils in patients in a clinic for severe asthma

Screening of clustered regulatory elements reveals functional cooperating dependencies in Leukemia

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate

Contact Info

Product

Resources

About