Unknown

Dataset Information

0

Purinergic P2X4 receptors and mitochondrial ATP production regulate T cell migration.


ABSTRACT: T cells must migrate in order to encounter antigen-presenting cells (APCs) and to execute their varied functions in immune defense and inflammation. ATP release and autocrine signaling through purinergic receptors contribute to T cell activation at the immune synapse that T cells form with APCs. Here, we show that T cells also require ATP release and purinergic signaling for their migration to APCs. We found that the chemokine stromal-derived factor-1? (SDF-1?) triggered mitochondrial ATP production, rapid bursts of ATP release, and increased migration of primary human CD4+ T cells. This process depended on pannexin-1 ATP release channels and autocrine stimulation of P2X4 receptors. SDF-1? stimulation caused localized accumulation of mitochondria with P2X4 receptors near the front of cells, resulting in a feed-forward signaling mechanism that promotes cellular Ca2+ influx and sustains mitochondrial ATP synthesis at levels needed for pseudopod protrusion, T cell polarization, and cell migration. Inhibition of P2X4 receptors blocked the activation and migration of T cells in vitro. In a mouse lung transplant model, P2X4 receptor antagonist treatment prevented the recruitment of T cells into allograft tissue and the rejection of lung transplants. Our findings suggest that P2X4 receptors are therapeutic targets for immunomodulation in transplantation and inflammatory diseases.

SUBMITTER: Ledderose C 

PROVIDER: S-EPMC6063471 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications


T cells must migrate in order to encounter antigen-presenting cells (APCs) and to execute their varied functions in immune defense and inflammation. ATP release and autocrine signaling through purinergic receptors contribute to T cell activation at the immune synapse that T cells form with APCs. Here, we show that T cells also require ATP release and purinergic signaling for their migration to APCs. We found that the chemokine stromal-derived factor-1α (SDF-1α) triggered mitochondrial ATP produc  ...[more]

Similar Datasets

| S-EPMC3441317 | biostudies-literature
| S-EPMC2939657 | biostudies-literature
| S-EPMC8738159 | biostudies-literature
| S-EPMC2981474 | biostudies-literature
| S-EPMC5037001 | biostudies-literature
| S-EPMC4881047 | biostudies-literature
| S-EPMC3260798 | biostudies-literature
| S-EPMC6138603 | biostudies-literature
| S-EPMC3564200 | biostudies-literature
| S-EPMC7340685 | biostudies-literature