# Integrins α3 and α6 promote Th17 cell migration by activating the purinergic receptor P2X4

## TL;DR

This study shows how Th17 cells use integrins α3 and α6 to migrate in laminin by triggering ATP release and activating the P2X4 receptor, which could influence immune responses and inflammation.

## Contribution

The study identifies a novel mechanism where integrins α3 and α6 promote Th17 cell migration via ATP release and P2X4 receptor activation.

## Key findings

- Laminin 10 induces ATP release through pannexin-1 hemichannels, which is essential for Th17 cell migration.
- The P2X4 receptor is crucial for Th17 cell migration, while P2X7 and P2Y11 receptors are not involved.
- Laminin 10 activates calcium entry in Th17 cells via the P2X4 receptor, enhancing migration.

## Abstract

Interactions of effector T cells with laminins during their trafficking across basement membranes play a crucial role in the development of the adaptive immune response and inflammatory diseases. However, the mechanisms involved in this process are not fully understood. In this study, we report that human Th17 cells express and use integrins α3 and α6 to migrate in laminin 10, which is predominant in basement membranes. We showed that laminin 10 induces via integrins α3 and α6, a sustained release of ATP from the mitochondria through pannexin-1 hemichannels, and that extracellular ATP is necessary for Th17 cell migration suggesting the implication of purinergic signaling. Inhibition studies identified a major role for the ionotropic purinergic receptor P2X4 in Th17 cell migration whereas purinergic receptors P2X7 and P2Y11 had no role. Along these lines, our results showed that laminin 10 induced calcium entry into Th17 cells via the P2X4 receptor. Together these results show that integrins α3 and α6 induce Th17 cell migration by activating the P2X4 receptor. Our findings uncovered a crosstalk between laminin-binding integrins and purinergic signaling in promoting human Th17 cell migration and suggest that this pathway can play an important role in the immune response.

This graphic shows how human Th17 cells migrate in laminin. Engagement of both laminin-binding integrins α3 and α6 by laminin 10 induces the release of ATP from the mitochondria through pannexin 1 channels. Extracellular ATP acts in an autocrine fashion to activate the purinergic receptor P2X4, which increases intracellular calcium. Calcium then enhances integrin activation and subsequently Th17 cell migration.