Human lung cDC1 drive increased perforin-mediated NK cytotoxicity in chronic obstructive pulmonary disease Article Swipe
Alexander M. Pallazola
,
Jessica X. Rao
,
D.T. Mengistu
,
Maria S. Morcos
,
M.S. Toma
,
Valerie R. Stolberg
,
Alexandra Tretyakova
,
Lisa McCloskey
,
Jeffrey L. Curtis
,
Christine M. Freeman
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1152/ajplung.00322.2020
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1152/ajplung.00322.2020
In chronic obstructive pulmonary disease (COPD), lung natural killer cells (NKs) lyse autologous lung epithelial cells in vitro, but underlying mechanisms and their relationship to epithelial cell apoptosis in vivo are undefined. Although this cytolytic capacity of lung NKs depends on priming by dendritic cells (DCs), whether priming correlates with DC maturation or is limited to a specific DC subset is also unknown. We recruited ever-smokers (≥10 pack-years; n = 96) undergoing clinically indicated lung resections. We analyzed lung NKs for cytotoxic molecule transcripts and for cytotoxicity, which we correlated with in situ detection of activated Caspase-3/7+ airway epithelial cells. To investigate DC priming, we measured lung DC expression of CCR2, CCR7, and CX3CR1 and cocultured peripheral blood NKs with autologous lung DCs, either matured using lipopolysaccharide (LPS) (nonobstructed smokers) or separated into conventional dendritic cell type-1 (cDC1) versus cDC type-2 (cDC2) (COPD). Lung NKs in COPD expressed more perforin ( P < 0.02) and granzyme B ( P < 0.03) transcripts; inhibiting perforin blocked in vitro killing by lung NKs. Cytotoxicity in vitro correlated significantly ( S r = 0.68, P = 0.0043) with numbers of apoptotic epithelial cells per airway. In nonobstructed smokers, LPS-induced maturation enhanced DC-mediated priming of blood NKs, reflected by greater epithelial cell death. Although CCR7 expression was greater in COPD in both cDC1 ( P < 0.03) and cDC2 ( P = 0.009), only lung cDC1 primed NK killing. Thus, rather than being intrinsic to those with COPD, NK priming is a capacity of human lung DCs that is inducible by recognition of bacterial (and possibly other) danger signals and restricted to the cDC1 subset.
Related Topics
Concepts
Priming (agriculture)
Lung
Perforin
Immunology
Medicine
COPD
Cytotoxic T cell
C-C chemokine receptor type 7
Cancer research
In vitro
Immune system
Biology
Chemokine
Internal medicine
CD8
Biochemistry
Chemokine receptor
Botany
Germination
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1152/ajplung.00322.2020
- OA Status
- green
- Cited By
- 15
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3208528949
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3208528949Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1152/ajplung.00322.2020Digital Object Identifier
- Title
-
Human lung cDC1 drive increased perforin-mediated NK cytotoxicity in chronic obstructive pulmonary diseaseWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-10-27Full publication date if available
- Authors
-
Alexander M. Pallazola, Jessica X. Rao, D.T. Mengistu, Maria S. Morcos, M.S. Toma, Valerie R. Stolberg, Alexandra Tretyakova, Lisa McCloskey, Jeffrey L. Curtis, Christine M. FreemanList of authors in order
- Landing page
-
https://doi.org/10.1152/ajplung.00322.2020Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/8715029Direct OA link when available
- Concepts
-
Priming (agriculture), Lung, Perforin, Immunology, Medicine, COPD, Cytotoxic T cell, C-C chemokine receptor type 7, Cancer research, In vitro, Immune system, Biology, Chemokine, Internal medicine, CD8, Biochemistry, Chemokine receptor, Botany, GerminationTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
15Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 6, 2023: 3, 2022: 3Per-year citation counts (last 5 years)
- References (count)
-
53Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| publication_year | 2021 |
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