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.

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.

Background/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals. Methods: We utilized proteomic profiling to analyze autoantibody reactivity against a broad spectrum of proteins expressed in lymphoid and myeloid cell subsets in serum samples from severe and moderate COVID-19 patients, as well as vaccinated individuals who received the inactivated CoronaVac (Sinovac) vaccine. Results: Our findings indicate a marked increase in the diversity and number of IgG autoantibodies targeting intracellular and membrane-associated proteins in severe COVID-19 cases, compared to those with moderate cases of the disease. The autoantibody response in severe cases was found to primarily target proteins involved in immune cell activation, signaling, and differentiation, suggesting potential pathways of immune dysregulation and autoimmunity. In contrast, vaccinated individuals did not exhibit similar autoantibody reactivity, pointing to a more controlled immune response post-vaccination. Notably, no significant autoimmune responses were detected in the vaccinated cohort, suggesting that the inactivated vaccine does not induce autoreactive IgG. These findings align with the established safety profile of COVID-19 vaccines, especially in comparison to the heightened immune dysregulation observed in severe COVID-19 patients. The absence of a significant autoantibody response in vaccinated individuals supports the notion that vaccines, while inducing robust immune activation, do not typically trigger autoimmunity in healthy individuals. Conclusions: Our study underscores the importance of distinguishing between the immune responses triggered by infection and vaccination and highlights the need for the continued monitoring of autoimmune responses in severe COVID-19 cases. Future research should focus on the long-term persistence and clinical relevance of these autoantibodies, particularly in individuals with pre-existing autoimmune conditions or genetic predispositions.

Santander L, et al. Clin Exp Vaccine Res. 2024 Jan;13(1):1-9. https://doi.org/10.7774/cevr.2024.13.1.1

Human T-lymphotropic virus type 1 (HTLV-1) infection is associated with a spectrum of clinical outcomes, ranging from lifelong asymptomatic carriage to severe conditions such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although antibody responses are known to shape immune regulation, the functional relevance of IgG idiotype repertoires in HTLV-1 pathogenesis remains poorly understood. This study investigated the immunomodulatory effects of IgG from individuals with distinct HTLV-1 clinical outcomes. IgG was purified from pooled serum samples of asymptomatic carriers (ACs), HAM/TSP, and ATLL patients and used to stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors. Cytokine production in CD4⁺, CD8⁺, and γδ T cells was assessed by flow cytometry. Additionally, proteome-wide IgG reactivity was evaluated using a human protein microarray encompassing over 21,000 proteins, and bioinformatic analyses were conducted to identify protein–protein interaction networks and tissue-specific autoreactivity. HAM/TSP-derived IgG selectively enhanced IFN-γ production in all T-cell subsets and suppressed IL-4 in CD4⁺ T cells. ATLL-derived IgG induced IL-9 and IL-13 production in CD4⁺ T cells, and both HAM/TSP and ATLL IgG elevated IL-13 levels in CD8⁺ T cells. Microarray data revealed distinct autoreactive IgG profiles across clinical groups, targeting immune-related proteins, apoptotic regulators, and proteins expressed in T cells, monocytes, and non-immune tissues such as brain and testis. Notably, no functional or structural clustering was observed in protein–protein interaction networks, suggesting these reactivities reflect complex, idiotype-specific immune alterations rather than compensatory responses. The present findings suggest that HTLV-1 infection may be associated with the development of distinct IgG repertoires that potentially modulate cytokine responses and exhibit broad reactivity toward human proteins. Such patterns could contribute to immune dysregulation and may partially explain the divergent clinical trajectories observed in HAM/TSP and ATLL. Further investigations are warranted to validate these observations at the individual level and to clarify their mechanistic relevance in disease progression.

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.