IgG from atopic dermatitis patients induces <scp>IL</scp>‐17 and <scp>IL</scp>‐10 production in infant intrathymic <scp>TCD</scp>4 and <scp>TCD</scp>8 cells

Sgnotto, Fábio da Ressureição; Oliveira, Marília Garcia de; Lira, Aline Aparecida de Lima; Inoue, Amanda Harumi Sabô; Titz, Tiago O.; Orfali, Raquel Leão; Bento-de-Souza, Luciana; Sato, Maria Notomi; Aoki, Valéria; Duarte, Alberto J. S.; Victor, Jefferson Russo

doi:10.1111/ijd.13907

Cited by 24 publications

(43 citation statements)

References 49 publications

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“…In this context, maternal antibodies may exert a function, but only a few evidences about this hypothesis can be found in the literature. Between then, antibodies inducing clonal deletion of thymocytes was demonstrated years ago and, more recently, a modulatory effect on T cells cytokine production was evidenced in human thymocytes . Until the present moment, no direct evidence of modulatory effects of antibodies on Tregs maturation is described.…”

Section: Discussionmentioning

confidence: 92%

Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition

et al. 2018

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The regulation of offspring allergy development mediated by maternal immunization was evidenced by several groups, and this mechanism seems to involve the induction of regulatory T cells (Tregs) on offspring. Here, we aimed to evaluate whether the effect of maternal immunization on offspring Tregs occurs as a result of peripheral or central modulation. Briefly, C57BL/6 female mice were immunized with OVA in Alum or Alum alone and boosted with OVA in saline or saline only after 10 and 20 days. Non-immunized offspring serum, thymus and spleen were evaluated at 3 or 20 days old, and some groups of pups were submitted to neonatal OVA-immunization protocol for the subsequent evaluation of antibody production and allergic response. Our experimental protocol could be validated because maternal OVA-immunization inhibited offspring allergic response as evidenced by the suppression of offspring IgE production and allergic lung inflammation. Interestingly, maternal immunization reduced the frequency of offspring thymic Tregs with an opposite effect on spleen Tregs. Furthermore, after neonatal immunization, the frequency of lung-infiltrated Tregs was also augmented on offspring from immunized mothers. In conclusion, maternal OVAimmunization can inhibit the thymic maturation of offspring Tregs without implications on peripheral Tregs induction and allergy inhibition.

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Section: Discussionmentioning

confidence: 92%

Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition

et al. 2018

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“…Extensive literature evidence demonstrates that the immune status of IgG donors may be related to differential modulation of thymic lymphocytes [ 26 , 31 , 45 , 46 ], which has been discussed in the literature since 2014 [ 6 , 47 ]. Among related observations, nonatopic IgG may be related to thymic maturation of lymphocytes with an allergy inhibition-related cytokine profile induced by γδT cells [ 48 ] as well as T CD4+ and CD8+ cells [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thymocyte separation was performed using Ficoll–Paque Plus (GE Healthcare, Danderyd, Sweden) after centrifugation as previously described [ 31 ]. Cell viability was assessed by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+ B Cells (B10) Revealed in a Pilot Study

Inoue

Lira

Oliveira

et al. 2020

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Regulatory B (B10) cells can control several inflammatory diseases, including allergies; however, the origin of peripheral B10 cells is not fully understood, and the involvement of primary lymphoid organs (PLOs) as a primary site of maturation is not known. Here, using a murine model of allergy inhibition mediated by maternal immunization with ovalbumin (OVA), we aimed to evaluate whether B10 cells can mature in the thymus and whether IgG can mediate this process. Female mice were immunized with OVA, and offspring thymus, bone marrow, spleen, lung, and serum samples were evaluated at different times and after passive transfer of purified IgG or thymocytes. A translational approach was implemented using human nonatopic thymus samples, nonatopic peripheral blood mononuclear cells (PBMCs), and IgG from atopic or nonatopic individuals. Based on the expression of CD1d on B cells during maturation stages, we suggest that B10 cells can also mature in the murine thymus. Murine thymic B10 cells can be induced in vitro and in vivo by IgG and be detected in the spleen and lungs in response to an allergen challenge. Like IgG from atopic individuals, human IgG from nonatopic individuals can induce B10 cells in the infant thymus and adult PBMCs. Our observations suggest that B10 cells may mature in the thymus and that this mechanism may be mediated by IgG in both humans and mice. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.

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“…It should also be mentioned that the IgG from AD patients has recently been described as a modulator of thymic TCD4 and TCD8 cells cytokine production, but the investigation of IgG effect in thymic iNKT cells is unprecedented in the literature, requiring further approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Our group had been discussing and demonstrating that IgG antibodies can exert a pivotal role mediating the modulation of lymphocytes cytokine production . In this context, we also demonstrated that IgG purified from atopic dermatitis (AD) patients can favor the production of IL‐17 and IL‐10 by thymic TCD4 and TCD8 cells . This approach collaborates with the elucidation of AD pathogenesis, but other cell populations also matured in the thymus can be related to AD development, including invariant natural killer T (iNKT) cells.…”

Section: Introductionmentioning

confidence: 90%

IgG from atopic dermatitis patients induces non‐atopic infant thymic invariant natural killer T (iNKT) cells to produce IL‐4, IL‐17, and IL‐10

et al. 2019

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Background Atopic dermatitis (AD) pathogenesis still needs to be elucidated, but invariant natural killer T (iNKT) cell involvement was already described by several groups. Our group has demonstrated that IgG antibodies purified from AD patients can modulate cytokine production by thymic T cells. Here we aimed to investigate if IgG from AD patients can modulate infant non-atopic thymic iNKT cells cytokine production in order to collaborate with the elucidation of AD development in infancy.Methods Thymic tissues were obtained from children from non-atopic mothers, and IgG was purified from AD patients diagnosed as moderate or severe and, as controls, from subjects clinically classified as non-atopic individuals. PBMCs from non-atopic individuals were also used in this study. ResultsOur results demonstrated that IgG from AD patients could induce non-atopic children thymic iNKT cells to produce higher levels of intracellular IL-4, IL-10, and IL-17 when compared to all control conditions. No effect was observed in non-atopic adults peripheral iNKT. We also observed that IgG from AD patients induces an increase in the expression of CD4 and Rorct transcription factor in non-atopic children thymic iNKT cells compared to the condition of all controls.Conclusions These observations suggest that IgG from AD patients can induce a cytokine profile by thymic iNKT cells from non-atopic infants compatible with the observations in AD development, which can collaborate with the elucidation of AD pathogenesis.

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IgG from atopic dermatitis patients induces IL‐17 and IL‐10 production in infant intrathymic TCD4 and TCD8 cells

Abstract: IgG of AD patients can stimulate cytokine production in infant thymocytes and thus resembles the peripheral profile observed in adults. These findings suggest a novel mechanism that can contribute to AD pathogenesis.

Cited by 24 publications

References 49 publications

Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition

Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition

The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+ B Cells (B10) Revealed in a Pilot Study

IgG from atopic dermatitis patients induces non‐atopic infant thymic invariant natural killer T (iNKT) cells to produce IL‐4, IL‐17, and IL‐10

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