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| Status |
Public on Dec 17, 2023 |
| Title |
Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background Impaired interferon response and allergic sensitisation may contribute to virus induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDC) play a key role in antiviral immunity as critical producers of type I interferons (IFN-I). pDC also express the high affinity IgE receptor (FcRI) through which IFN-I production may be negatively regulated. If antiviral function of pDC is associated with recurrent episodes of wheeze in young children is not well understood. This study aimed to evaluate the phenotype and function of circulating pDC in children with a longitudinally defined wheezing phenotype.
Methods We performed multiparameter flow cytometry on peripheral blood mononuclear cells from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDC from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database.
Results We observed a significant depletion of circulating pDC in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the IgE receptor (FcRI) on their pDC. Based on transcriptomic analysis, pDC from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a non-recurrent wheezing phenotype.
Conclusion Our data suggests that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of FcRI is increased and their function as major IFN producers is impaired during acute exacerbations of wheeze.
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| Overall design |
Clinical samples obtained children with an acute respiratory wheeze, control samples were sampled from children in the community
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| Web link |
https://doi.org/10.1016/j.jaci.2023.11.920
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| Contributor(s) |
Coenen I, de Jong E, Jones AC, Khoo K, Foo S, Wu Howland S, Ginhoux F, Le Souëf P, Holt PG, Strickland DH, Laing I, Leffler J |
| Citation(s) |
38110059 |
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| Submission date |
Sep 13, 2023 |
| Last update date |
Mar 18, 2024 |
| Contact name |
Jonatan Leffler |
| E-mail(s) |
jonatan.leffler@telethonkids.org.au
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| Phone |
0439246262
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| Organization name |
Telethon Kids Institute
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| Street address |
15 Hospital Ave
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| City |
Nedlands |
| State/province |
WA |
| ZIP/Postal code |
6009 |
| Country |
Australia |
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| Platforms (1) |
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| Samples (38)
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| GSM7777933 |
human_study participant_4, control |
| GSM7777934 |
human_study participant_5, acute |
| GSM7777935 |
human_study participant_6, control |
| GSM7777936 |
human_study participant_7, control |
| GSM7777937 |
human_study participant_8, acute |
| GSM7777938 |
human_study participant_9, acute |
| GSM7777939 |
human_study participant_10, acute |
| GSM7777940 |
human_study participant_11, acute |
| GSM7777941 |
human_study participant_12, control |
| GSM7777942 |
human_study participant_13, control |
| GSM7777943 |
human_study participant_14, acute |
| GSM7777944 |
human_study participant_15, control |
| GSM7777945 |
human_study participant_16, acute |
| GSM7777946 |
human_study participant_17, control |
| GSM7777947 |
human_study participant_18, acute |
| GSM7777948 |
human_study participant_19, control |
| GSM7777949 |
human_study participant_20, acute |
| GSM7777950 |
human_study participant_21, acute |
| GSM7777951 |
human_study participant_22, acute |
| GSM7777952 |
human_study participant_23, control |
| GSM7777953 |
human_study participant_24, acute |
| GSM7777954 |
human_study participant_25, control |
| GSM7777955 |
human_study participant_26, acute |
| GSM7777956 |
human_study participant_27, acute |
| GSM7777957 |
human_study participant_28, control |
| GSM7777958 |
human_study participant_29, acute |
| GSM7777959 |
human_study participant_30, acute |
| GSM7777960 |
human_study participant_31, acute |
| GSM7777961 |
human_study participant_32, acute |
| GSM7777962 |
human_study participant_33, acute |
| GSM7777963 |
human_study participant_34, control |
| GSM7777964 |
human_study participant_35, acute |
| GSM7777965 |
human_study participant_36, acute |
| GSM7777966 |
human_study participant_37, acute |
| GSM7777967 |
human_study participant_38, control |
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| Relations |
| BioProject |
PRJNA1016300 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE243052_processed_data.csv.gz |
4.1 Mb |
(ftp)(http) |
CSV |
| GSE243052_raw_counts.csv.gz |
1.4 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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