Preconceptional immunization with an allergen inhibits offspring thymic Th17 cells maturation without influence on Th1 and Th2 cells

Oliveira, Marília Garcia de; Sgnotto, Fábio da Ressureição; Sousa, Thamires Rodrigues de; Fagundes, Beatriz Oliveira; Duarte, Alberto José da Silva; Victor, Jefferson Russo

doi:10.1684/ecn.2020.0452

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…As theoretically discussed in 2017 with the "MatIgG primary modulation theory" (35), the passive transference of maternal IgG can modulate offspring immunity when maternal IgG reaches offspring primary organs modulating the immunity development according to maternal atopic state. This hypothesis has been confirmed with pieces of evidence obtained in murine (36,37) and translational experimental approaches (38,39).…”

Section: Discussionsupporting

confidence: 59%

IgG from atopic individuals can mediate non atopic infant thymic and adult peripheral CD8 TC2 skewing without influence on TC17 or TC22 cells

Sousa

Sgnotto

Fagundes

et al. 2020

Eur Ann Allergy Clin Immunol

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The potential of IgG antibodies as allergy regulators has been discussed for decades and was brought to light that anti-allergen IgG is related to allergy inhibition in children during the first years of life and that IgG repertoire can differ between atopic and non-atopic individuals. Here, we aimed to evaluate in vitro the differential effects of purified IgG from atopic and non-atopic individuals on the production of IL-4, IL-17, and IL-22 by human intra-thymic and mature peripheral CD8 + T cells respectively termed as TC2, TC17, and TC22 cells. We additionally evaluated the IFN-γ production by CD8 + T cells. Thereupon we used infants thymic tissues from non-atopic mothers and blood samples from individuals clinically classified as non-atopic. Thymocytes or PBMCs were cultured with IgG from atopic or non-atopic individuals. As controls, we used commercial IgG (Intravenous immunoglobulin -IVIg) or mock condition. The phenotype and intracellular cytokine production were evaluated using flow cytometry. IgG from atopic individuals could increase the frequency of TC2 cells in non-atopic infant thymic and adult peripheral cell cultures compared to all control conditions. Due to the TC2 cell's potential to collaborate with pathology and severity of asthma in humans, this evidence can cooperate with the understanding of the development of an atopic state.

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Section: Discussionsupporting

confidence: 59%

IgG from atopic individuals can mediate non atopic infant thymic and adult peripheral CD8 TC2 skewing without influence on TC17 or TC22 cells

Sousa

Sgnotto

Fagundes

et al. 2020

Eur Ann Allergy Clin Immunol

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“…Hence, observing human and murine studies that correlate the modulatory effect of IgG according to its repertoire in allergies [ 16 , 17 , 19 , 20 , 33 , 34 ], HIV-1 infection [ 13 ], and AD [ 20 , 21 ], we hypothesized that IgG from AD patients could be elected as a biological-inducing factor naturally developed by individuals prone to develop AD. To test this hypothesis, we used a standardized protocol of human thymic culture with IgG to investigate the effect of adults’ AD IgG repertoire on non-atopic infant thymus, focusing on the production of a Th22 profile and expression of the skin-homing molecule CLA [ 5 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…The debate over the mechanisms implicated in the modulatory effect of IgG on the thymic maturation of T cells has intensified in the last years [ 8 , 9 , 10 ], but there is still scarce evidence to explain the molecular basis of this process/hypothesis. Several studies have reported that different IgG antibody repertoires can play a pivotal role in mediating thymic and peripheral lymphocytes in murine and humans [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In AD, it has been reported that IgG from AD patients could favor the production of IL-17 and IL-10 by neonatal thymic CD4 and CD8 T cells and induce the expression of IL-4, IL-17, and IL-10 by neonatal thymic iNKT cells [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA

Sousa

Fagundes

Nascimento

et al. 2022

IJMS

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Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-γ, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can collaborate in thymic T cells in the setting of infant AD.

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“…Mainly, this influence can be related to passive transference of maternal anti-allergen IgG and the peripheral inhibition of offspring Th2 related cytokines and IgE production [ 8 , 9 , 10 , 11 ]. Nevertheless, when analyzing the influence of maternal IgG on an offspring primary organ as the thymus, it could be observed that the maternal influence can affect Th17 cells without influence on Th1 and Th2 cells [ 12 ] and, due to biological similarities, can also involve the maturation of IL-17-producing γδ T [ 13 ]. The involvement of IL-17 producing γδT cells have been discussed in the main clinical manifestations of allergic diseases [ 14 , 15 , 16 ], and the modulatory effect of murine maternal allergen immunization on offspring thymic IL-17 producing γδT cells thymus was suggested to mediate this effect in mouse and human [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Some hypotheses discussed that maternal immunization with allergens could broadly modulate offspring intrathymic maturation of T cells [ 18 , 19 , 20 ] and had been experimentally evidenced for murine and human γδT, Treg and Breg cells [ 12 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. However, no molecular pieces of evidence have been obtained to elucidate if this mechanism involves some epigenetic alterations on modulated cells.…”

Section: Introductionmentioning

confidence: 99%

Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

de-Sousa

Pessôa

Nascimento

et al. 2021

IJMS

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The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing γδT cells in offspring thymus, and if this mechanism has epigenetic implications mediated by microRNAs (miRNAs) expression. Wild-type (WT) C57BL/6 females were immunized with OVA in Alum or Alum alone and were mated with normal WT males. Evaluating their offspring thymus at 3 or 20 days old (d.o.), we observed that maternal OVA immunization could inhibit the thymic frequency of offspring CD27- and IL-17+ γδT cells at the neonatal and until 20 days old. Furthermore, we evaluated the expression of function-related γ and δ variable γδTCR chains (Vγ1, Vγ2, Vγ3, Vδ4, and Vδ6.3), observing that maternal OVA-immunization inhibits Vγ2 chains expression. The small RNAs (sRNAs), particularly miRNAs, and messenger RNAs (mRNA) expression profiles by pools of thymus tissue samples (from 9 to 11 mice) from offspring OVA-immunized or Alum-immunized mothers were analyzed via Illumina sequencing platform and bioinformatics approaches. Using a fold change >4, our results showed that seven miRNAs (mmu-miR-126a-3p, 101a-3p, 744-3p,142-5p, 15a-5p, 532-5p, and 98-5p) were differentially expressed between both groups. Ten target genes were predicted to interact with the seven selected miRNAs. There were no enriched categories of gene ontology functional annotation and pathway enrichment analysis for the target genes. Interestingly, four of the identified miRNAs (mmu-miR-15a, mmu-miR-101 mmu-miR-126, and mmu-miR-142) are related to IL-17 production. Our data is of significance because we demonstrate that maternal immunization can modulate offspring thymic maturation of IL-17-producing γδT cells possibly by an epigenetic mechanism mediated by miRNAs.

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Preconceptional immunization with an allergen inhibits offspring thymic Th17 cells maturation without influence on Th1 and Th2 cells

Cited by 6 publications

References 31 publications

IgG from atopic individuals can mediate non atopic infant thymic and adult peripheral CD8 TC2 skewing without influence on TC17 or TC22 cells

IgG from atopic individuals can mediate non atopic infant thymic and adult peripheral CD8 TC2 skewing without influence on TC17 or TC22 cells

IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA

Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

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