<scp><i>STAT6</i></scp> polymorphisms are associated with neonatal regulatory <scp>T</scp> cells and cytokines and atopic diseases at 3 years

Casaca, Vera Isabel; Illi, Sabina; Klucker, E.; Ballenberger, Nikolaus; Schedel, Michaela; Mutius, Erika von; Kabesch, Michael; Schaub, Bianca

doi:10.1111/all.12220

Cited by 23 publications

(18 citation statements)

References 36 publications

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“…Moreover, up‐regulation of activation markers on circulating Tregs in adult AD is also well documented . In contrast, in paediatric AD, there are fewer studies and the findings are more controversial . Contradictory results may be explained, in part, by the effects different treatments (eg, cyclosporine, glucocorticoids, UV irradiation) have on Tregs .…”

Section: Discussionmentioning

confidence: 99%

“…22 In contrast, in paediatric AD, there are fewer studies and the findings are more controversial. 46,47 Contradictory results may be explained, in part, by the effects different treatments (eg, cyclosporine, glucocorticoids, UV irradiation) have on Tregs. 17 Thus, in this study, to circumvent age-and treatment-related bias, we recruited exclusively adult patients with no history of AD therapy.…”

Section: Discussionmentioning

confidence: 99%

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Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis

Moosbrugger‐Martinz

Gruber

Ladstätter

et al. 2018

J Cellular Molecular Medi

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Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis. Although regulatory T cells (Tregs) have previously been studied in AD, their role remains controversial, likely owing to patient heterogeneity. Thus, we recruited adult AD patients and age‐matched healthy controls, and assessed their filaggrin (FLG) genotype, serum IgE level, and eczema area and severity index (EASI). We found increased proportions of all circulating Treg subpopulations in AD patients. Moreover, we show positive correlations between circulating Tregs and serum IgE FLG null mutations limited the expansion of both memory and effector Tregs and enhanced that of recently thymus‐emigrated Tregs. Furthermore, proportions of circulating Th2‐ or Th17‐Tregs but not Th1‐Tregs were increased in AD patients, and accentuated by FLG null mutations, thereby mimicking the immune deviation observed in Th cell populations. Moreover, ICOS+ Tregs showed reduced production of interleukin‐10, suggesting impaired immunosuppression in AD. The level of demethylation of FOXP3i1, which reflects the stability of FOXP3 expression, was similar in the blood and skin of AD patients and healthy controls. Overall, these results show that Tregs may participate into AD pathogenesis and that FLG null mutations exert further modifications on specific subpopulations of circulating Tregs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis

Moosbrugger‐Martinz

Gruber

Ladstätter

et al. 2018

J Cellular Molecular Medi

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“…STAT6 variants were found to be associated with AD [57,58]. Neonates with the rs324011 polymorphism in the STAT6 had a lower risk of AD as they showed a reduced number of regulatory T cells (Tregs) and an increased Th1 response at birth [59]. A common haplotype encoding IL-31 was shown to be a risk factor for intrinsic AD.…”

Section: Geneticsmentioning

confidence: 99%

“…As mentioned above, GATA-3 plays important roles in the generation and function of ILCs [223]. A recent GWAS of severe AD found new loci including candidate genes that may contribute to the defects in GATA-3 and STAT6 [59,227,228]. …”

Section: Immunological Abnormalitiesmentioning

confidence: 99%

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

Kim

Cho

et al. 2016

IJMS

110

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Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology.

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“…Allergy occurs in people with atopy; defined as “a genetic predisposition toward the development of immediate hypersensitivity reactions against common environmental antigens” (3). It is a polygenic disorder linked to polymorphisms in genes of cytokine, cytokine receptors, and transcription factors associated with Th2 immune responses and with the expression of IgE and its receptors (4–7). In contrast, the elevated Th2 cytokines, IgE and eosinophilia during helminth infection are normal physiological responses to these pathogens.…”

Section: The Ige Response Is a Physiological Immune Response To Helmimentioning

confidence: 99%

Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity

2014

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The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.g., EF-hand proteins, tropomyosin, and PR-1 proteins). During some helminth infection, especially with the well adapted hookworm, the Th2 response is moderated by parasite-expressed molecules. This has been associated with reduced allergy in helminth endemic areas and worm infection or products have been proposed as treatments for allergic conditions. However, some infections (especially Ascaris) are associated with increased allergy and this has been linked to cross-reactivity between worm proteins (e.g., tropomyosins) and highly similar molecules in dust-mites and insects. The overlap between allergy and helminth infection is best illustrated in Anisakis simplex, a nematode that when consumed in under-cooked fish can be both an infective helminth and a food allergen. Nearly 20 molecular allergens have been isolated from this species, including tropomyosin (Ani s 3) and the EF-hand protein, Ani s troponin. In this review, we highlight aspects of the biology and biochemistry of helminths that may have influenced the evolution of the IgE response. We compare dominant IgE-antigens in worms with clinically important environmental allergens and suggest that arrays of such molecules will provide important information on anti-worm immunity as well as allergy.

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STAT6 polymorphisms are associated with neonatal regulatory T cells and cytokines and atopic diseases at 3 years

Cited by 23 publications

References 36 publications

Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis

Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity

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