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IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD

Briend, Emmanuel; Ferguson, G. John; Mori, Michiko LU ; Damera, Gautam; Stephenson, Katherine; Karp, Natasha A.; Sethi, Sanjay; Ward, Christine K; Sleeman, Matthew A. and Erjefält, Jonas S. LU , et al. (2017) In Respiratory Research 18(1).
Abstract

Background: Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. Methods: The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. Results: We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key... (More)

Background: Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. Methods: The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. Results: We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Conclusions: Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.

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published
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keywords
Chronic obstructive pulmonary disease, Interferon gamma, Interleukin-18, Lymphocytes, Lymphoid aggregates, Tertiary follicles
in
Respiratory Research
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85028022167
  • pmid:28830544
ISSN
1465-9921
DOI
10.1186/s12931-017-0641-7
language
English
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yes
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d1b8d881-9e90-40eb-80ef-81e1c48e53dd
date added to LUP
2017-09-04 11:26:24
date last changed
2017-09-05 03:00:14
@article{d1b8d881-9e90-40eb-80ef-81e1c48e53dd,
  abstract     = {<p>Background: Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. Methods: The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. Results: We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Conclusions: Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.</p>},
  articleno    = {159},
  author       = {Briend, Emmanuel and Ferguson, G. John and Mori, Michiko and Damera, Gautam and Stephenson, Katherine and Karp, Natasha A. and Sethi, Sanjay and Ward, Christine K and Sleeman, Matthew A. and Erjefält, Jonas S. and Finch, Donna K.},
  issn         = {1465-9921},
  keyword      = {Chronic obstructive pulmonary disease,Interferon gamma,Interleukin-18,Lymphocytes,Lymphoid aggregates,Tertiary follicles},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Respiratory Research},
  title        = {IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD},
  url          = {http://dx.doi.org/10.1186/s12931-017-0641-7},
  volume       = {18},
  year         = {2017},
}