1. Immunology and Inflammation
  2. Medicine

Perinatal granulopoiesis and risk of pediatric asthma

  1. Benjamin A Turturice  Is a corresponding author
  2. Juliana Theorell
  3. Mary Dawn Koenig
  4. Lisa Tussing-Humphreys
  5. Diane R Gold
  6. Augusto A Litonjua
  7. Emily Oken
  8. Sheryl L Rifas-Shiman
  9. David L Perkins  Is a corresponding author
  10. Patricia W Finn  Is a corresponding author
  1. University of Illinois at Chicago, United States
  2. Brigham and Women's Hospital, Harvard Medical School, United States
  3. University of Rochester, United States
  4. Harvard Medical School and Harvard Pilgrim Health Care Institute, United States
https://doi.org/10.7554/eLife.63745
Share this article
Cite this article
  1. Benjamin A Turturice
  2. Juliana Theorell
  3. Mary Dawn Koenig
  4. Lisa Tussing-Humphreys
  5. Diane R Gold
  6. Augusto A Litonjua
  7. Emily Oken
  8. Sheryl L Rifas-Shiman
  9. David L Perkins
  10. Patricia W Finn
(2021)
Perinatal granulopoiesis and risk of pediatric asthma
eLife 10:e63745.
https://doi.org/10.7554/eLife.63745
  2. Download BibTeX
  3. Download .RIS

Abstract

There are perinatal characteristics, such as gestational age, reproducibly associated with risk for pediatric asthma. Identification of biologic processes influenced by these characteristics could facilitate risk stratification or new therapeutic targets. We hypothesized that transcriptional changes associated with multiple epidemiologic risk factors would be mediators of pediatric asthma risk. Using publicly available transcriptomic data from cord blood mononuclear cells, transcription of genes involved in myeloid differentiation were observed to be inversely associated with a pediatric asthma risk stratification based on multiple perinatal risk factors. This gene signature was validated in an independent prospective cohort and was specifically associated with genes localizing to neutrophil specific granules. Further validation demonstrated that umbilical cord blood serum concentration of PGLYRP-1, a specific granule protein, was inversely associated with mid-childhood current asthma and early-teen FEV1/FVCx100. Thus, neutrophil specific granule abundance at birth predicts risk for pediatric asthma and pulmonary function in adolescence.

Data availability

Data from RNAseq is available on NCBI Bioproject database PRJNA577955.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Benjamin A Turturice

    Department of Microbiology and Immunology, Department of Medicine, University of Illinois at Chicago, Chicago, United States
    For correspondence
    bturtu2@uic.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9382-4612

  2. Juliana Theorell

    Department of Medicine, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Mary Dawn Koenig

    Department of Women, Children and Family Health Science, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Lisa Tussing-Humphreys

    Department of Medicine and Cancer Center, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Diane R Gold

    Channing Division of Network Medicine, Department of Medicine, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Augusto A Litonjua

    Department of Pediatrics, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Emily Oken

    Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Sheryl L Rifas-Shiman

    Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. David L Perkins

    Department of Medicine, University of Illinois at Chicago, Chicago, United States
    For correspondence
    perkinsd@uic.edu
    Competing interests
    The authors declare that no competing interests exist.

  10. Patricia W Finn

    Department of Microbiology and Immunology, Department of Medicine, Department of Bioengineering, University of Illinois at Chicago, Chicago, United States
    For correspondence
    pwfinn@uic.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Heart, Lung, and Blood Institute (F30HL136001)

  • Benjamin A Turturice

National Institute of Allergy and Infectious Diseases (R01AI053878)

  • Patricia W Finn

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD034568)

  • Emily Oken

National Institutes of Health (UH3OD023286)

  • Emily Oken

Robert Wood Johnson Foundation (Nurse Faculty Scholars Program #72117)

  • Mary Dawn Koenig

University of Illinois at Chicago (College of Nursing Dean's Award)

  • Mary Dawn Koenig

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The current study was approved by the University of Illinois at Chicago IRB, 20160326 and 20150353, and the IRB of Harvard Pilgrim Health Care.

Copyright

© 2021, Turturice et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,498
    views
  • 130
    downloads
  • 2
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Benjamin A Turturice
  2. Juliana Theorell
  3. Mary Dawn Koenig
  4. Lisa Tussing-Humphreys
  5. Diane R Gold
  6. Augusto A Litonjua
  7. Emily Oken
  8. Sheryl L Rifas-Shiman
  9. David L Perkins
  10. Patricia W Finn
(2021)
Perinatal granulopoiesis and risk of pediatric asthma
eLife 10:e63745.
https://doi.org/10.7554/eLife.63745

Share this article

https://doi.org/10.7554/eLife.63745

Categories and tags

Research organism

Further reading

    1. Immunology and Inflammation

    RAG suppresses group 2 innate lymphoid cells

    Aaron M Ver Heul, Madison Mack ... Brian S Kim
    Research Article

    Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the function of innate natural killer (NK) cells, whether other innate immune cells such as ILC2s are affected by RAG remains unclear. We find that in RAG-deficient mice, ILC2 populations expand and produce increased IL-5 and IL-13 at steady state and contribute to increased inflammation in atopic dermatitis (AD)-like disease. Furthermore, we show that RAG modulates ILC2 function in a cell-intrinsic manner independent of the absence or presence of adaptive T and B lymphocytes. Lastly, employing multiomic single cell analyses of RAG1 lineage-traced cells, we identify key transcriptional and epigenomic ILC2 functional programs that are suppressed by a history of RAG expression. Collectively, our data reveal a novel role for RAG in modulating innate type 2 immunity through suppression of ILC2s.

    1. Immunology and Inflammation

    Bacterial Clearance: With a little help from T cells

    Troy Burtchett, Neal Hammer
    Insight

    Specific host factors, such as immune cell activity, sex hormones and microbiota composition, influence the ability of Staphylococcus aureus bacteria to colonize the gut of mice.

    1. Immunology and Inflammation
    2. Neuroscience

    Microglia aging in the hippocampus advances through intermediate states that drive activation and cognitive decline

    Jeremy M Shea, Saul A Villeda
    Research Article

    During aging, microglia – the resident macrophages of the brain – exhibit altered phenotypes and contribute to age-related neuroinflammation. While numerous hallmarks of age-related microglia have been elucidated, the progression from homeostasis to dysfunction during the aging process remains unresolved. To bridge this gap in knowledge, we undertook complementary cellular and molecular analyses of microglia in the mouse hippocampus across the adult lifespan and in the experimental aging model of heterochronic parabiosis. Single-cell RNA-Seq and pseudotime analysis revealed age-related transcriptional heterogeneity in hippocampal microglia and identified intermediate states of microglial aging that also emerge following heterochronic parabiosis. We tested the functionality of intermediate stress response states via TGFβ1 and translational states using pharmacological approaches in vitro to reveal their modulation of the progression to an activated state. Furthermore, we utilized single-cell RNA-Seq in conjunction with in vivo adult microglia-specific Tgfb1 conditional genetic knockout mouse models to demonstrate that microglia advancement through intermediate aging states drives transcriptional inflammatory activation and hippocampal-dependent cognitive decline.