The differential expression of IL-4 and IL-13 and its impact on type-2 immunity

Bao, Katherine; Reinhardt, R. Lee

doi:10.1016/j.cyto.2015.05.008

Cited by 259 publications

(204 citation statements)

References 232 publications

(258 reference statements)

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“…However, basophils, eosinophils, and NK cells can also produce IL-13 [137]. The only report concerning autistic patients showed increased plasma levels of IL-13 [115].…”

Section: Interleukin 13mentioning

confidence: 99%

Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid

Deckmann

Schwingel

Fontes-Dutra

et al. 2018

Neuroimmunomodulation

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Autism spectrum disorder (ASD) is a highly prevalent developmental disorder characterized by deficits in communication and social interaction and in stereotyped or repetitive behaviors. Besides the classical behavioral dyad, several comorbidities are frequently present in patients with ASD, such as anxiety, epilepsy, sleep disturbances, and gastrointestinal tract dysfunction. Although the etiology of ASD remains unclear, there is supporting evidence for the involvement of both genetic and environmental factors. Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring. The animal model of autism induced by prenatal exposure to VPA demonstrates important structural and behavioral features that can be observed in individuals with autism; it is thus an excellent tool for testing new drug targets and developing novel behavioral and drug therapies. In addition, immunological alterations during pregnancy could affect the developing embryo because immune molecules can pass through the placental barrier. In fact, exposure to pathogens during the pregnancy is a known risk factor for ASD, and maternal immune activation can lead to autistic-like features in animals. Interestingly, neuroimmune alterations are common in both autistic individuals and in animal models of ASD. We summarize here the important alterations in inflammatory markers, such as cytokines and chemokines, in patients with ASD and in the VPA animal model.

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“…However, basophils, eosinophils, and NK cells can also produce IL-13 [137]. The only report concerning autistic patients showed increased plasma levels of IL-13 [115].…”

Section: Interleukin 13mentioning

confidence: 99%

Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid

Deckmann

Schwingel

Fontes-Dutra

et al. 2018

Neuroimmunomodulation

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show abstract

“…In contrast, allergic asthma and allergies often result from the improper activation of type-2 inflammation. Recent studies posit that type-2 immune responses are divided into two distinct arms (2–4). One arm is modulated by canonical T-helper (Th) 2 cells, which promote innate cell recruitment, mucus production, smooth muscle contractility, and tissue remodeling at mucosal barriers.…”

Section: Introductionmentioning

confidence: 99%

BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity

Bao

Carr

et al. 2016

The Journal of Immunology

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The AP-1 factor, basic leucine zipper transcription factor, ATF-like (BATF) is important for CD4+ T-helper (Th) 17, Th9 and follicular T helper (Tfh) cell development. However, its precise role in Th2 differentiation and function remains unclear, and the necessity of BATF in non-allergic settings of type-2 immunity has not been explored. Here, we show that in response to parasitic helminths, Batf−/− mice are unable to generate both Tfh and Th2 cells. As a consequence, Batf−/− mice fail to establish productive type-2 immunity during primary and secondary infection. Batf−/− CD4+ T cells do not achieve type-2 cytokine competency, which implies that BATF plays a key role in the regulation of interleukin(IL)-4 and IL-13. In contrast to Th17 and Th9 cell subsets where BATF binds directly to promoter and enhancer regions to regulate cytokine expression, our results show that BATF is significantly enriched at Rad50 hypersensitivity sites (RHS) 6 and 7 of the locus control region (LCR) relative to AP-1 sites surrounding type-2 cytokine loci in Th2 cells. Indeed, Batf−/− CD4+ T cells do not obtain permissive epigenetic modifications within the Th2 locus, which have been linked to RHS6 and RHS7 function. In sum, these findings reveal BATF as a central modulator of peripheral and humoral hallmarks of type-2 immunity, and begin to elucidate a novel mechanism by which BATF regulates type-2 cytokine production through its modification of the Th2 LCR.

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“…Different subsets of T cells (including CD4 + , CD8 + , γδ, and dendritic epidermal T cells, or DETCs), mast cells, basophils, type 2 innate lymphoid (ILC2) cells, eosinophils, natural killer (NK) cells, natural killer T (NKT) cells, monocytes, and neutrophils have been shown to express IL‐4 and/or IL‐13 during allergic inflammation (Bao & Reinhardt, 2015; Chen et al., 2014; Sun et al., 2018; Vantourout & Hayday, 2013; von Bubnoff et al., 2010). To address whether these and other cell types express IL‐4 or IL‐13 in the skin after MC903 treatment, we wanted to quantify these cell subsets and various macrophage subpopulations, as they are known to be responsive to type 2 cytokines.…”

Section: Commentarymentioning

confidence: 99%

Panel Design and Optimization for High‐Dimensional Immunophenotyping Assays Using Spectral Flow Cytometry

et al. 2020

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Technological advances in fluorescence flow cytometry and an ever‐expanding understanding of the complexity of the immune system have led to the development of large (20+ parameters) flow cytometry panels. However, as panel complexity and size increase, so does the difficulty involved in designing a high‐quality panel, accessing the instrumentation capable of accommodating large numbers of parameters, and analyzing such high‐dimensional data. A recent advancement is spectral flow cytometry, which in contrast to conventional flow cytometry distinguishes the full emission spectrum of each fluorophore across all lasers, rather than identifying only the peak of emission. Fluorophores with a similar emission maximum but distinct off‐peak signatures can therefore be accommodated within the same flow cytometry panel, allowing greater flexibility in terms of panel design and fluorophore detection. Here, we highlight the specific characteristics of spectral flow cytometry and aim to guide users through the process of building, designing, and optimizing high‐dimensional spectral flow cytometry panels using a comprehensive step‐by‐step protocol. Special considerations are also given for using highly overlapping dyes, and a logical selection process for optimal marker‐fluorophore assignment is provided. © 2020 by John Wiley & Sons, Inc.

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The differential expression of IL-4 and IL-13 and its impact on type-2 immunity

Cited by 259 publications

References 232 publications

Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid

Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid

BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity

Panel Design and Optimization for High‐Dimensional Immunophenotyping Assays Using Spectral Flow Cytometry

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