IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma–Delta T Cells (γδT) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA

Abstract

γδT cells mature in the human thymus, and mainly produce IL-17A or IFN-γ, but can also produce IL-22 and modulate a variety of immune responses. Here, we aimed to evaluate whether IgG from AD patients (AD IgG) can functionally modulate thymic nonatopic γδT cells. Thymic tissues were obtained from 12 infants who had not had an atopic history. Thymocytes were cultured in mock condition, or in the presence of either AD IgG or therapeutic intravenous IgG (IVIg). Following these treatments, intracellular cytokine production, phenotype, and microRNA expression profiles were investigated. AD IgG could downregulate α4β7, upregulate CLA, and induce the production of IFN-γ, IL-17, and IL-22 in γδT cells. Although both AD IgG and IVIg could directly interact with γδT cell membranes, AD IgG could reduce γδT cell apoptosis. AD IgG could upregulate nine miRNAs compared to IVIg, and six when compared to the mock condition. In parallel, some miRNAs were downregulated. Target gene prediction and functional analysis indicated that some target genes were enriched in the negative regulation of cellular transcription. This study shows that AD IgG influences the production of IL-17 and IL-22 by intrathymic nonatopic γδT cells, and demonstrates epigenetic implications mediated by miRNAs.

Immune modulation and possible pathological implications mediated by naturally produced immunoglobulin G idiotypes: from historical to recent experimental and clinical studies focused on atopic dermatitis

“…This study assessed the effect of IgG from AD patients on non-atopic neonatal thymic γδT cells and demonstrated that IgG from AD patients could downregulate the expression of α4β7 and up-regulate the expression of CLA homing molecules on γδT cells. This study suggested that IgG from AD patients may exert some role in modulating homing properties of T cells during its maturation on the thymus, inducing a skin-homing profile (CLA+), which may corroborate with the elucidation of AD development [ 32 ]. Additionally, the same study demonstrated that IgG from AD patients induced the production of IFN-γ, IL-17, and IL-22 and reduced the apoptosis on thymic γδT cells, corroborating not only with a skin-homing profile but also a cytokine secretion profile and an anti-apoptotic profile that may play some role on AD development.…”

IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction

“…Previously, our research group demonstrated that the human thymus can generate IL-10-producing regulatory B cells (B10) in response to stimulation with polyclonal IgG from individuals with allergies 18 . In recent years, the immunomodulatory effects of polyclonal IgG have been observed both in vitro 30 – 34 and in vivo 35 – 38 , primarily focusing on T cell populations in murine and human systems.…”

Gender Differences in microRNA Expressions as Related to Long-Term Graft Function in Kidney Transplant Patients

“…Studies have shown that differences in hormones and genes are considered to have an impact on both disease and health status [ 3 ]. Recently, expressions of miRNAs have been particularly highlighted due to their various effects on downstream signal pathways [ 5 ], including immuno-related cytokines [ 6 ]. To explain the reason for generally worse long-term outcomes in female KTx patients, we investigated the pathology of kidney graft injuries and collected data regarding immune-related serum miRNA to study the possible correlation.…”

“…Studies have shown that differences in hormones and genes are considered to have an impact on diseases and health status [ 3 , 4 ]. Recently, expressions of microRNA (miRNA) have been particularly highlighted due to its various effects on downstream signal pathways [ 5 ], including proinflammatory cytokines and anti-inflammatory cytokines [ 6 ]. MiRNAs are groups of non-coding RNAs possessing essential cellular functions such as cell proliferation, cell differentiation, organ development and immuno-regulation [ 7 ].…”