Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

Matthew C. Altman, Michelle A Gill, Elizabeth Whalen, Denise C. Babineau, Baomei Shao, Andrew H. Liu, Brett Jepson, Rebecca S Gruchalla, George T. O’Connor, Jacqueline A. Pongracic, Carolyn M. Kercsmar, Gurjit K. Khurana Hershey, Edward M. Zoratti, Christine C. Johnson, Stephen J. Teach, Meyer Kattan, Leonard B. Bacharier, Avraham Beigelman, Steve M. Sigelman, Scott Presnell & 6 others James E. Gern, Peter J. Gergen, Lisa M. Wheatley, Alkis Togias, William W. Busse, Daniel J. Jackson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.

Original languageEnglish (US)
Pages (from-to)637-651
Number of pages15
JournalNature Immunology
Volume20
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Transcriptome
Asthma
Viruses
Mucus
Epidermal Growth Factor Receptor
Eosinophils
Respiratory Tract Infections
Extracellular Matrix
Up-Regulation
Down-Regulation
Epithelial Cells
Lymphocytes
Infection
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Altman, M. C., Gill, M. A., Whalen, E., Babineau, D. C., Shao, B., Liu, A. H., ... Jackson, D. J. (2019). Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children. Nature Immunology, 20(5), 637-651. https://doi.org/10.1038/s41590-019-0347-8

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children. / Altman, Matthew C.; Gill, Michelle A; Whalen, Elizabeth; Babineau, Denise C.; Shao, Baomei; Liu, Andrew H.; Jepson, Brett; Gruchalla, Rebecca S; O’Connor, George T.; Pongracic, Jacqueline A.; Kercsmar, Carolyn M.; Khurana Hershey, Gurjit K.; Zoratti, Edward M.; Johnson, Christine C.; Teach, Stephen J.; Kattan, Meyer; Bacharier, Leonard B.; Beigelman, Avraham; Sigelman, Steve M.; Presnell, Scott; Gern, James E.; Gergen, Peter J.; Wheatley, Lisa M.; Togias, Alkis; Busse, William W.; Jackson, Daniel J.

In: Nature Immunology, Vol. 20, No. 5, 01.05.2019, p. 637-651.

Research output: Contribution to journalArticle

Altman, MC, Gill, MA, Whalen, E, Babineau, DC, Shao, B, Liu, AH, Jepson, B, Gruchalla, RS, O’Connor, GT, Pongracic, JA, Kercsmar, CM, Khurana Hershey, GK, Zoratti, EM, Johnson, CC, Teach, SJ, Kattan, M, Bacharier, LB, Beigelman, A, Sigelman, SM, Presnell, S, Gern, JE, Gergen, PJ, Wheatley, LM, Togias, A, Busse, WW & Jackson, DJ 2019, 'Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children', Nature Immunology, vol. 20, no. 5, pp. 637-651. https://doi.org/10.1038/s41590-019-0347-8
Altman, Matthew C. ; Gill, Michelle A ; Whalen, Elizabeth ; Babineau, Denise C. ; Shao, Baomei ; Liu, Andrew H. ; Jepson, Brett ; Gruchalla, Rebecca S ; O’Connor, George T. ; Pongracic, Jacqueline A. ; Kercsmar, Carolyn M. ; Khurana Hershey, Gurjit K. ; Zoratti, Edward M. ; Johnson, Christine C. ; Teach, Stephen J. ; Kattan, Meyer ; Bacharier, Leonard B. ; Beigelman, Avraham ; Sigelman, Steve M. ; Presnell, Scott ; Gern, James E. ; Gergen, Peter J. ; Wheatley, Lisa M. ; Togias, Alkis ; Busse, William W. ; Jackson, Daniel J. / Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children. In: Nature Immunology. 2019 ; Vol. 20, No. 5. pp. 637-651.
@article{fdc46d4866e14c7cace7920dc6537728,
title = "Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children",
abstract = "Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.",
author = "Altman, {Matthew C.} and Gill, {Michelle A} and Elizabeth Whalen and Babineau, {Denise C.} and Baomei Shao and Liu, {Andrew H.} and Brett Jepson and Gruchalla, {Rebecca S} and O’Connor, {George T.} and Pongracic, {Jacqueline A.} and Kercsmar, {Carolyn M.} and {Khurana Hershey}, {Gurjit K.} and Zoratti, {Edward M.} and Johnson, {Christine C.} and Teach, {Stephen J.} and Meyer Kattan and Bacharier, {Leonard B.} and Avraham Beigelman and Sigelman, {Steve M.} and Scott Presnell and Gern, {James E.} and Gergen, {Peter J.} and Wheatley, {Lisa M.} and Alkis Togias and Busse, {William W.} and Jackson, {Daniel J.}",
year = "2019",
month = "5",
day = "1",
doi = "10.1038/s41590-019-0347-8",
language = "English (US)",
volume = "20",
pages = "637--651",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

AU - Altman, Matthew C.

AU - Gill, Michelle A

AU - Whalen, Elizabeth

AU - Babineau, Denise C.

AU - Shao, Baomei

AU - Liu, Andrew H.

AU - Jepson, Brett

AU - Gruchalla, Rebecca S

AU - O’Connor, George T.

AU - Pongracic, Jacqueline A.

AU - Kercsmar, Carolyn M.

AU - Khurana Hershey, Gurjit K.

AU - Zoratti, Edward M.

AU - Johnson, Christine C.

AU - Teach, Stephen J.

AU - Kattan, Meyer

AU - Bacharier, Leonard B.

AU - Beigelman, Avraham

AU - Sigelman, Steve M.

AU - Presnell, Scott

AU - Gern, James E.

AU - Gergen, Peter J.

AU - Wheatley, Lisa M.

AU - Togias, Alkis

AU - Busse, William W.

AU - Jackson, Daniel J.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.

AB - Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.

UR - http://www.scopus.com/inward/record.url?scp=85064074102&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064074102&partnerID=8YFLogxK

U2 - 10.1038/s41590-019-0347-8

DO - 10.1038/s41590-019-0347-8

M3 - Article

VL - 20

SP - 637

EP - 651

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 5

ER -