High-dimensional analysis of the aging immune system: Verification of age-associated differences in immune signaling res
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RESEARCH
Open Access
High-dimensional analysis of the aging immune system: Verification of age-associated differences in immune signaling responses in healthy donors Diane M Longo1, Brent Louie1, Jason Ptacek1, Greg Friedland1, Erik Evensen1, Santosh Putta1, Michelle Atallah1, David Spellmeyer1, Ena Wang2,3, Zoltan Pos4, Francesco M Marincola2,3, Andrea Schaeffer5, Suzanne Lukac5, Radha Railkar5, Chan R Beals5, Alessandra Cesano1, Leonidas N Carayannopoulos5 and Rachael E Hawtin1*
Abstract Background: Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. Methods: In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25–40 yrs)]. Results: Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. Conclusions: These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies. Keywords: Multi-parameter flow cytometry, Systems immunology, Aging, Immune signaling
Background Due to an age-related decline in the function of the immune system, the elderly are more susceptible to infectious diseases and less likely to mount a sufficient response to vaccination [1,2]. However, the mechanisms underlying immunosenescence are incompletely understood. While mouse models have helped to reveal age-associated defects in T cells [3], due to species-specific differences in immunological aging, scientific findings in mice do not always translate directly to humans [4]. Recent studies of age-related immunological defects in human samples have been highly focused on characterizing age-associated changes in T cells [5]. Thus, such studies are often
performed on purified T cells or T cell subsets, which precludes the identification of age-associated changes in the multitude of immune cell types intentionally removed/ depleted from the purified sample. Further, traditional immunological studies often utilize population-level approaches such as Western blots which fail to capture heterogeneity within the cell population/subpopulation under scrutiny. A systems biology approach capable of capturi
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