Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10450270" target="_blank" >RIV/00064203:_____/23:10450270 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/23:10450270
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rqESIU3WJj" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rqESIU3WJj</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.clim.2022.109174" target="_blank" >10.1016/j.clim.2022.109174</a>
Alternative languages
Result language
angličtina
Original language name
Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility
Original language description
STAT1 gain-of-function (GOF) mutations underlie an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). Beyond the fungal susceptibility, attributed to Th17 failure, over half of the reported patients suffer from autoimmune manifestations, mechanism of which has not been explained yet. We hypothesized that the STAT1 mutations would affect dendritic cells' (DCs) properties and alter their inflammatory and tolerogenic functions. To test the hypothesis, we generated monocyte-derived DCs (moDCs) and tolerogenic DCs (tDCs). Functional and signaling studies, co-culture experiments and RNA sequencing demonstrated that STAT1 GOF DCs were profoundly altered in their phenotype and functions, characterized by loss of tolerogenic functions, proinflammatory skew and decreased capacity to induce Th17. Cytokine signaling, autophagy and metabolic processes were identified as the most prominently altered cellular processes. The results suggest that DCs are directly involved in STAT1 GOF-associated immune pathology, possibly contributing to both autoimmune manifestations and the failure of antifungal defense.
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
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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
Clinical Immunology
ISSN
1521-6616
e-ISSN
1521-7035
Volume of the periodical
246
Issue of the periodical within the volume
January
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
109174
UT code for WoS article
000972927000001
EID of the result in the Scopus database
2-s2.0-85142138782