The receptor-type protein tyrosine phosphatase CD45 promotes onset and severity of IL-1β–mediated autoinflammatory osteomyelitis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F21%3A10440407" target="_blank" >RIV/00216208:11310/21:10440407 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gZ1Aipo5yF" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gZ1Aipo5yF</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2021.101131" target="_blank" >10.1016/j.jbc.2021.101131</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The receptor-type protein tyrosine phosphatase CD45 promotes onset and severity of IL-1β–mediated autoinflammatory osteomyelitis

Popis výsledku v původním jazyce

A number of human autoinflammatory diseases manifest with severe inflammatory bone destruction. Mouse models of these diseases represent valuable tools that help us to understand molecular mechanisms triggering this bone autoinflammation. The Pstpip2(cmo) mouse strain is among the best characterized of these; it harbors a mutation resulting in the loss of adaptor protein PSTPIP2 and development of autoinflammatory osteomyelitis. In Pstpip2(cmo) mice, overproduction of interleukin-1 beta (IL-1β) and reactive oxygen species by neutrophil granulocytes leads to spontaneous inflammation of the bones and surrounding soft tissues. However, the upstream signaling events leading to this overproduction are poorly characterized. Here, we show that Pstpip2(cmo) mice deficient in major regulator of Src-family kinases (SFKs) receptor-type protein tyrosine phosphatase CD45 display delayed onset and lower severity of the disease, while the development of autoinflammation is not affected by deficiencies in Toll-like receptor signaling. Our data also show deregulation of pro-IL-1β production by Pstpip2(cmo) neutrophils that are attenuated by CD45 deficiency. These data suggest a role for SFKs in autoinflammation. Together with previously published work on the involvement of protein tyrosine kinase spleen tyrosine kinase,they point to the role of receptors containing immunoreceptor tyrosine-based activation motifs, which after phosphorylation by SFKs recruit spleen tyrosine kinase for further signal propagation.We propose that this class of receptors triggers the events resulting in increased pro-IL-1β synthesis and disease initiation and/or progression.

Název v anglickém jazyce

The receptor-type protein tyrosine phosphatase CD45 promotes onset and severity of IL-1β–mediated autoinflammatory osteomyelitis

Popis výsledku anglicky

A number of human autoinflammatory diseases manifest with severe inflammatory bone destruction. Mouse models of these diseases represent valuable tools that help us to understand molecular mechanisms triggering this bone autoinflammation. The Pstpip2(cmo) mouse strain is among the best characterized of these; it harbors a mutation resulting in the loss of adaptor protein PSTPIP2 and development of autoinflammatory osteomyelitis. In Pstpip2(cmo) mice, overproduction of interleukin-1 beta (IL-1β) and reactive oxygen species by neutrophil granulocytes leads to spontaneous inflammation of the bones and surrounding soft tissues. However, the upstream signaling events leading to this overproduction are poorly characterized. Here, we show that Pstpip2(cmo) mice deficient in major regulator of Src-family kinases (SFKs) receptor-type protein tyrosine phosphatase CD45 display delayed onset and lower severity of the disease, while the development of autoinflammation is not affected by deficiencies in Toll-like receptor signaling. Our data also show deregulation of pro-IL-1β production by Pstpip2(cmo) neutrophils that are attenuated by CD45 deficiency. These data suggest a role for SFKs in autoinflammation. Together with previously published work on the involvement of protein tyrosine kinase spleen tyrosine kinase,they point to the role of receptors containing immunoreceptor tyrosine-based activation motifs, which after phosphorylation by SFKs recruit spleen tyrosine kinase for further signal propagation.We propose that this class of receptors triggers the events resulting in increased pro-IL-1β synthesis and disease initiation and/or progression.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Svazek periodika

297

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

101131

Kód UT WoS článku

000713100000010

EID výsledku v databázi Scopus

2-s2.0-85115411488