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- Consiglio, Camila, et al.
(author)
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Immune system adaptation during gender-affirming testosterone treatment
- 2023
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In: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
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Journal article (other academic/artistic)abstract
- Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.
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3. |
- Tajvar, Pouria, 1991-, et al.
(author)
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Modelling Pathogen Response of the Human Immune System in a Reduced State Space
- 2023
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In: 2023 62nd IEEE Conference on Decision and Control, CDC 2023. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 715-720
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Conference paper (peer-reviewed)abstract
- The immune system response to pathogens is organized by a network of cells communicating through expression of a variety of proteins and signaling molecules. A high number of genes are involved in encoding these communicating agents, but the relatively low number of data points is a major challenge in modelling the gene expression response. In this work we propose a feature-selection approach based on gene expression distributions at the single-cell level that improves dynamics identification at the population level. We investigate common approaches to differential expression analysis and show that Earth Mover's Distance (EMD) is a relatively robust measure for gene selection as reflected by the coefficient of variation as well as accuracy of a naive Bayes classifier based on the selected genes. We ultimately propose the bootstrap standard deviation metric as an estimate of state uncertainty and show that statistically significant signals in pathogen response can be recovered in the reduced state space constructed with the selected genes.
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