imprint:
American Association for the Advancement of Science (AAAS), 2022
Published in:Science Advances
Language:
English
DOI:
10.1126/sciadv.abl9770
ISSN:
2375-2548
Origination:
Footnote:
Description:
<jats:p>
Initial T cell activation is triggered by the formation of highly dynamic, spatiotemporally restricted Ca
<jats:sup>2+</jats:sup>
microdomains. Purinergic signaling is known to be involved in Ca
<jats:sup>2+</jats:sup>
influx in T cells at later stages compared to the initial microdomain formation. Using a high-resolution Ca
<jats:sup>2+</jats:sup>
live-cell imaging system, we show that the two purinergic cation channels P2X4 and P2X7 not only are involved in the global Ca
<jats:sup>2+</jats:sup>
signals but also promote initial Ca
<jats:sup>2+</jats:sup>
microdomains tens of milliseconds after T cell stimulation. These Ca
<jats:sup>2+</jats:sup>
microdomains were significantly decreased in T cells from
<jats:italic>
P2rx4
<jats:sup>−/−</jats:sup>
</jats:italic>
and
<jats:italic>
P2rx7
<jats:sup>−/−</jats:sup>
</jats:italic>
mice or by pharmacological inhibition or blocking. Furthermore, we show a pannexin-1–dependent activation of P2X4 in the absence of T cell receptor/CD3 stimulation. Subsequently, upon T cell receptor/CD3 stimulation, ATP release is increased and autocrine activation of both P2X4 and P2X7 then amplifies initial Ca
<jats:sup>2+</jats:sup>
microdomains already in the first second of T cell activation.
</jats:p>