| First Author | Frascoli M | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 1 | Pages | 174-80 |
| PubMed ID | 22649196 | Mgi Jnum | J:188945 |
| Mgi Id | MGI:5442653 | Doi | 10.4049/jimmunol.1101582 |
| Citation | Frascoli M, et al. (2012) Purinergic P2X7 receptor drives T cell lineage choice and shapes peripheral gammadelta cells. J Immunol 189(1):174-80 |
| abstractText | TCR signal strength instructs alphabeta versus gammadelta lineage decision in immature T cells. Increased signal strength of gammadeltaTCR with respect to pre-TCR results in induction of the gammadelta differentiation program. Extracellular ATP evokes physiological responses through purinergic P2 receptors expressed in the plasma membrane of virtually all cell types. In peripheral T cells, ATP released upon TCR stimulation enhances MAPK activation through P2X receptors. We investigated whether extracellular ATP and P2X receptors signaling tuned TCR signaling at the alphabeta/gammadelta lineage bifurcation checkpoint. We show that P2X7 expression was selectively increased in immature gammadelta(+)CD25(+) cells. These cells were much more competent to release ATP than pre-TCR-expressing cells following TCR stimulation and Ca(2+) influx. Genetic ablation as well as pharmacological antagonism of P2X7 resulted in impaired ERK phosphorylation, reduction of early growth response (Egr) transcripts induction, and diversion of gammadeltaTCR-expressing thymocytes toward the alphabeta lineage fate. The impairment of the ERK-Egr-inhibitor of differentiation 3 (Id3) signaling pathway in gammadelta cells from p2rx7(-/-) mice resulted in increased representation of the Id3-independent NK1.1-expressing gammadelta T cell subset in the periphery. Our results indicate that ATP release and P2X7 signaling upon gammadeltaTCR expression in immature thymocytes constitutes an important costimulus in T cell lineage choice through the ERK-Egr-Id3 signaling pathway and contributes to shaping the peripheral gammadelta T cell compartment. |
