Neutrophils in STAT1 Gain-Of-Function Have a Pro-inflammatory Signature Which Is Not Rescued by JAK Inhibition
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F23%3A10465378" target="_blank" >RIV/00216208:11130/23:10465378 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/23:10465378
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.nhk-BEkqn" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.nhk-BEkqn</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s10875-023-01528-1" target="_blank" >10.1007/s10875-023-01528-1</a>
Alternative languages
Result language
angličtina
Original language name
Neutrophils in STAT1 Gain-Of-Function Have a Pro-inflammatory Signature Which Is Not Rescued by JAK Inhibition
Original language description
STAT1 gain-of-function (GOF) mutations cause an inborn error of immunity with diverse phenotype ranging from chronic mucocutaneous candidiasis (CMC) to various non-infectious manifestations, the most precarious of which are autoimmunity and vascular complications. The pathogenesis centers around Th17 failure but is far from being understood. We hypothesized that neutrophils, whose functions have not been explored in the context of STAT1 GOF CMC yet, might be involved in the associated immunodysregulatory and vascular pathology. In a cohort of ten patients, we demonstrate that STAT1 GOF human ex-vivo peripheral blood neutrophils are immature and highly activated; have strong propensity for degranulation, NETosis, and platelet-neutrophil aggregation; and display marked inflammatory bias. STAT1 GOF neutrophils exhibit increased basal STAT1 phosphorylation and expression of IFN stimulated genes, but contrary to other immune cells, STAT1 GOF neutrophils do not display hyperphosphorylation of STAT1 molecule upon stimulation with IFNs. The patient treatment with JAKinib ruxolitinib does not ameliorate the observed neutrophil aberrations. To our knowledge, this is the first work describing features of peripheral neutrophils in STAT1 GOF CMC. The presented data suggest that neutrophils may contribute to the immune pathophysiology of the STAT1 GOF CMC.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
<a href="/en/project/NU23-07-00170" target="_blank" >NU23-07-00170: Analysis of patterns of abnormal leukocyte signaling in childhood diseases using mass cytometry and machine learning.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Clinical Immunology
ISSN
0271-9142
e-ISSN
1573-2592
Volume of the periodical
43
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
1640-1659
UT code for WoS article
001013333700001
EID of the result in the Scopus database
2-s2.0-85162967038