Allergic Asthma Responses Are Dependent on Macrophage Ontogeny
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
The ontogenetic composition of tissue-resident macrophages following injury, environmental exposure, or experimental depletion can be altered upon re-establishment of homeostasis. However, the impact of altered resident macrophage ontogenetic milieu on subsequent immune responses is poorly understood. Hence, we assessed the effect of macrophage ontogeny alteration following return to homeostasis on subsequent allergic airway responses to house dust mites (HDM). Using lineage tracing, we confirmed alveolar and interstitial macrophage ontogeny and their replacement by bone marrow-derived macrophages following LPS exposure. This alteration in macrophage ontogenetic milieu reduced allergic airway responses to HDM challenge. In addition, we defined a distinct population of resident-derived interstitial macrophages expressing allergic airway disease genes, located adjacent to terminal bronchi, and reduced by prior LPS exposure. These findings support that the ontogenetic milieu of pulmonary macrophages is a central factor in allergic airway responses and has implications for how prior environmental exposures impact subsequent immune responses and the development of allergy.
### Competing Interest Statement
The authors have declared no competing interest.
* Abbreviations
:
AHR
: Airway hyper-responsiveness
AMØ
: Alveolar macrophage
IMØ
: Interstitial macrophage
T2
: T helper type 2
HDM
: House dust mite
o.p.
: Oropharyngeal aspiration
MCh
: Acetyl-β-methacholine
Rrs
: Respiratory system resistance
Ers
: Respiratory system elastance
Rn
: Newtonian resistance
G
: Tissue damping
H
: Tissue elastance
BALF
: Bronchoalveolar lavage fluid
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关键词
allergic asthma,macrophage ontogeny
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