Variation of Immune Cell Responses in Humans Reveals Sex-Specific Coordinated Signaling Across Cell Types

Abstract

Assessing the health and competence of the immune system is central to evaluating vaccination responses, autoimmune conditions, cancer prognosis, and treatment. With an increasing number of studies examining immune dysregulation, there is a growing need for a curated reference of variation in immune parameters in healthy individuals. We used mass cytometry (CyTOF) to profile blood from 86 humans in response to 15 ex vivo immune stimuli. We present reference ranges for cell-specific immune markers and highlight differences that appear across sex and age. We identified modules of immune features that suggest there exists an underlying structure to the immune system based on signaling pathway responses across cell types. We observed increased MAPK signaling in inflammatory pathways in innate immune cells and greater overall coordination of immune cell responses in females. In contrast, males exhibited stronger pSTAT1 and pTBK1 responses. These reference data are publicly available as a resource for immune profiling studies.

A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates

“…The submitted dataset may be viewed online, and the accompanying article by Fragiadakis, et al. ( 17 ) provides a detailed analysis of the human data, including correlations with demographics and signaling networks.…”

“…Here we show that there are conserved and differential qualities between species that must be carefully considered based on their relevance to the experiment at hand and provide a reference of these characteristics between species. The submitted dataset may be viewed online, and the accompanying article by Fragiadakis, et al (17) provides a detailed analysis of the human data, including correlations with demographics and signaling networks.…”

“…The complementary manuscript by Fragiadakis et al. ( 17 ) analyzes the human dataset in detail, including an examination of demographic differences, presenting a reference for human immune profiling studies. The entirety of the immunophenotyping and signaling dataset is available online at (accession FR-FCM-Z2ZY).…”

“…We present an overview of this cross-species analysis here, including several examples of specific differences between species. The complementary manuscript by Fragiadakis et al (17) analyzes the human dataset in detail, including an examination of demographic differences, presenting a reference for human immune profiling studies. The entirety of the immunophenotyping and signaling dataset is available online at https://flowrepository.org (accession FR-FCM-Z2ZY).…”

Exogenous Metals Atlas in Spermatozoa at Single-Cell Resolution in Relation to Human Semen Quality

“…Recently, CyTOF has been widely used for the simultaneous detection of multiple biomarkers in a single cell to identify immune cell type, cell differentiation, and cell responses in basic medical fields. 25,26 In the present study, we conducted a high-throughput analysis of multiple exogenous metals in spermatozoa at singlecell resolution by taking advantage of CyTOF technology and explored the associations between heterogeneous features of exogenous metals and human semen quality among 84 men screened as sperm donors who provided 266 semen samples within 90 days.…”