Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11130/23:10450270

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility

Popis výsledku v původním jazyce

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&apos; (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.

Název v anglickém jazyce

Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility

Popis výsledku anglicky

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&apos; (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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical Immunology

ISSN

1521-6616

e-ISSN

1521-7035

Svazek periodika

246

Číslo periodika v rámci svazku

January

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

109174

Kód UT WoS článku

000972927000001

EID výsledku v databázi Scopus

2-s2.0-85142138782