Smooth-talking T cells leave asthma breathless

Abstract

The plasma membrane channel PANX1 mediates release of bio-active adenine nucleotides; however, its function in immune cells is unknown. In this issue of Immunity, Medina et al. show that PANX1 mediates adenosine-dependent communication between regulatory and effector CD4⁺ T cells during allergic airway inflammation.

Figure 1.. A SIK1-PANX1 axis mediates extracellular adenosine-driven Treg and Teff cell communication and suppression of allergic airway inflammation

(Left) CD4⁺ Teff and Treg cells express SIK kinases, PANX1, CD39, CD73, and A2A adenosine receptors. Upon challenge with house-dust mite (HDM), SIK proteins phosphorylate S205 (mouse), or S206 (human) of PANX1 on CD4⁺ T cells. In both Treg and Teff cells, activated PANX1 releases extracellular ATP, which is catabolized by ecto-enzymes CD39 and CD73 to extracellular adenosine. Extracellular adenosine activates immune-suppressive adenosine A2A receptors on Teff and Treg cells, suppressing allergic airway inflammation. (Right) PANX1 deficiency or mutation on both CD4⁺ Teff and Treg cells lowers extracellular adenosine amounts during allergic airway inflammation. Lower amounts of extracellular adenosine reduce immune-suppressive A2AR signaling on Teff and pomotes allergic airway inflammation.