Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00604440" target="_blank" >RIV/68378050:_____/24:00604440 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/24:10490215

Výsledek na webu

<a href="https://academic.oup.com/jleukbio/article/117/1/qiae184/7742416" target="_blank" >https://academic.oup.com/jleukbio/article/117/1/qiae184/7742416</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/jleuko/qiae184" target="_blank" >10.1093/jleuko/qiae184</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation

Popis výsledku v původním jazyce

The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into the role of in T cell immunity, focusing on T cell-B cell conjugate formation and T cell activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes in Jurkat T cells, we identified BAP1 as a key positive regulator of T cell-B cell conjugate formation. Subsequent investigations into BAP1 knockout cells revealed impaired T cell activation, evidenced by decreased MAPK and NF-kB signaling pathways and reduced CD69 expression upon T cell receptor stimulation. Flow cytometry and qPCR analyses demonstrated that BAP1 deficiency leads to decreased surface expression of T cell receptor complex components and reduced mRNA levels of the co-stimulatory molecule CD28. Notably, the observed phenotypes associated with BAP1 knockout are specific to T cells and fully dependent on BAP1 catalytic activity. In-depth RNA-seq and mass spectrometry analyses further revealed that BAP1 deficiency induces broad mRNA and protein expression changes. Overall, our findings elucidate the vital role of BAP1 in T cell biology, especially in T cell-B cell conjugate formation and T cell activation, offering new insights and directions for future research in immune regulation.

Název v anglickém jazyce

Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation

Popis výsledku anglicky

The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into the role of in T cell immunity, focusing on T cell-B cell conjugate formation and T cell activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes in Jurkat T cells, we identified BAP1 as a key positive regulator of T cell-B cell conjugate formation. Subsequent investigations into BAP1 knockout cells revealed impaired T cell activation, evidenced by decreased MAPK and NF-kB signaling pathways and reduced CD69 expression upon T cell receptor stimulation. Flow cytometry and qPCR analyses demonstrated that BAP1 deficiency leads to decreased surface expression of T cell receptor complex components and reduced mRNA levels of the co-stimulatory molecule CD28. Notably, the observed phenotypes associated with BAP1 knockout are specific to T cells and fully dependent on BAP1 catalytic activity. In-depth RNA-seq and mass spectrometry analyses further revealed that BAP1 deficiency induces broad mRNA and protein expression changes. Overall, our findings elucidate the vital role of BAP1 in T cell biology, especially in T cell-B cell conjugate formation and T cell activation, offering new insights and directions for future research in immune regulation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/GA22-18046S" target="_blank" >GA22-18046S: Molekulární mechanismy T-lymfocytární paměti</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Journal of Leukocyte Biology

ISSN

0741-5400

e-ISSN

1938-3673

Svazek periodika

117

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

qiae184

Kód UT WoS článku

001307957700001

EID výsledku v databázi Scopus

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