Objective: The role of different immune cells in autism spectrum disorders (ASD) is still controversial. The purpose of this study was to evaluate the causal effects of different immune cell phenotypes on ASD via Mendelian randomization (MR).
Methods: Datasets of immune cell phenotypes were obtained from the European Bioinformatics Institute, and datasets of ASD were obtained from the IEU Open GWAS project. Single nucleotide polymorphisms were selected based on the assumptions of association, independence, and exclusivity. Inverse variance weighted was utilized as the main method for MR analysis. MR-Egger was employed to assess the horizontal pleiotropy of the results. Cochran's Q and leave-one-out method were used for heterogeneity analysis and sensitivity analysis of the results, respectively.
Results: MR analysis showed that TD CD8br AC [odds ratio (OR), 1.137; 95% confidence interval (CI), 1.031-1.254; = 0.010], CD8br %leukocyte (OR, 1.142; 95% CI, 1.067-1.223; < 0.001), CD8br and CD8dim %leukocyte (OR, 1.117; 95% CI, 1.032-1.210; = 0.006), naive CD8br %T cell (OR, 1.052; 95% CI, 1.004-1.104; = 0.035), CD28- CD8dim %T cell (OR, 1.097; 95% CI, 1.038-1.158; < 0.001), CD127- CD8br AC (OR, 1.086; 95% CI, 1.006-1.171; = 0.034), CD45 on CD8br (OR, 1.059; 95% CI, 1.021-1.099; = 0.002), CD3 on HLA DR+ CD8br (OR, 1.098; 95% CI, 1.041-1.158; < 0.001), CD4 on activated Treg (OR, 1.048; 95% CI, 1.001-1.096; = 0.046), CD3 on CD39+ resting Treg (OR, 1.070; 95% CI, 1.012-1.131; = 0.018), IgD+ CD38- %lymphocyte (OR, 1.103; 95% CI, 1.023-1.190; = 0.011), CD62L- plasmacytoid DC %DC (OR, 1.046; 95% CI, 1.001-1.093; = 0.046), and FSC-A on plasmacytoid DC (OR, 1.075; 95% CI, 1.003-1.153; = 0.042) were associated with increased genetic susceptibility to ASD. MR-Egger displayed no horizontal pleiotropy ( ≥ 0.05). Cochran's Q revealed no heterogeneity of results ( ≥ 0.05). Sensitivity analysis indicated that the results were robust.
Conclusion: This MR analysis revealed 13 immune cell phenotypes associated with increased genetic susceptibility to ASD and emphasized the importance of CD8 T cells and Tregs, which provides new directions for the pathogenesis and drug research of ASD.
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http://dx.doi.org/10.3389/fpsyt.2024.1397006 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139.
Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.
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January 2025
Center for Nutritional Sciences, Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611.
Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen 52074, Germany.
Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.
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January 2025
Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress.
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January 2025
Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.
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