Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation

Diane M. Longo, Brent Louie, Santosh Putta, Erik Evensen, Jason Ptacek, James Cordeiro, Ena Wang, Zoltan Pos, Rachael E. Hawtin, Francesco M. Marincola, Alessandra Cesano

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

A greater understanding of the function of the human immune system at the single-cell level in healthy individuals is critical for discerning aberrant cellular behavior that occurs in settings such as autoimmunity, immunosenescence, and cancer. To achieve this goal, a systems-level approach capable of capturing the response of the interdependent immune cell types to external stimuli is required. In this study, an extensive characterization of signaling responses in multiple immune cell subpopulations within PBMCs from a cohort of 60 healthy donors was performed using single-cell network profiling (SCNP). SCNP is a multiparametric flow cytometry-based approach that enables the simultaneous measurement of basal and evoked signaling in multiple cell subsets within heterogeneous populations. In addition to establishing the interindividual degree of variation within a broad panel of immune signaling responses, the possible association of any observed variation with demographic variables including age and race was investigated. Using half of the donors as a training set, multiple age- and race-associated variations in signaling responses in discrete cell subsets were identified, and several were subsequently confirmed in the remaining samples (test set). Such associations may provide insight into age-related immune alterations associated with high infection rates and diminished protection following vaccination and into the basis for ethnic differences in autoimmune disease incidence and treatment response. SCNP allowed for the generation of a functional map of healthy immune cell signaling responses that can provide clinically relevant information regarding both the mechanisms underlying immune pathological conditions and the selection and effect of therapeutics.

Original languageEnglish
Pages (from-to)1717-1725
Number of pages9
JournalJournal of Immunology
Volume188
Issue number4
DOIs
Publication statusPublished - 15 Feb 2012
Externally publishedYes

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Blood Cells
Tissue Donors
Therapeutic Uses
Autoimmunity
Autoimmune Diseases
Immune System
Flow Cytometry
Vaccination
Demography
Incidence
Infection
Population
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation. / Longo, Diane M.; Louie, Brent; Putta, Santosh; Evensen, Erik; Ptacek, Jason; Cordeiro, James; Wang, Ena; Pos, Zoltan; Hawtin, Rachael E.; Marincola, Francesco M.; Cesano, Alessandra.

In: Journal of Immunology, Vol. 188, No. 4, 15.02.2012, p. 1717-1725.

Research output: Contribution to journalArticle

Longo, Diane M. ; Louie, Brent ; Putta, Santosh ; Evensen, Erik ; Ptacek, Jason ; Cordeiro, James ; Wang, Ena ; Pos, Zoltan ; Hawtin, Rachael E. ; Marincola, Francesco M. ; Cesano, Alessandra. / Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation. In: Journal of Immunology. 2012 ; Vol. 188, No. 4. pp. 1717-1725.
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