Figure 3. P2X₇R signalling during infection and inflammation.

P2X₇R is required for mounting an appropriate inflammatory response to defend against invading pathogens, for example during intracellular killing of Mycobacterium tuberculosis by macrophages. Dying tumour cells release ATP, which activates P2X₇R expressed on DCs, which in turn promotes the priming of IFN-γ-producing cytotoxic CD8⁺ T cells that kill cancer cells. On the other hand, P2X₇R signalling on DCs and concomitant T-cell priming contributes to allergic disease states, such as CD8⁺ T-cell-elicited contact dermatitis. DC-mediated T-cell priming under the control of P2X₇R signalling has also been shown to promote T_H1 responses that are implicated in graft-versus-host disease, which contributes to the rejection of a transplanted organ. Similarly, P2X₇R-mediated T-cell priming towards a T_H2 response promotes allergic airway disease during asthma. Priming of T_H17 cells is critical during psoriasis and contributes to intestinal inflammation as occurs during IBD. P2X₇R signalling on enteric neurons or mast cells has been implicated in promoting intestinal inflammation during IBD.