The P2X7 Receptor in Autoimmunity

Abstract

The P2X7 receptor (P2X7R) is an ATP-gated nonselective cationic channel that, upon intense stimulation, can progress to the opening of a pore permeable to molecules up to 900 Da. Apart from its broad expression in cells of the innate and adaptive immune systems, it is expressed in multiple cell types in different tissues. The dual gating property of P2X7R is instrumental in determining cellular responses, which depend on the expression level of the receptor, timing of stimulation, and microenvironmental cues, thus often complicating the interpretation of experimental data in comprehensive settings. Here we review the existing literature on P2X7R activity in autoimmunity, pinpointing the different functions in cells involved in the immunopathological processes that can make it difficult to model as a druggable target.

Keywords: T cells; autoantibodies; autoimmunity; purinergic signaling.

Figure 1

Function of P2X7R in autoimmunity. The diagram shows the general functions of P2X7R in innate and adaptive immunity (center) and peculiar pathogenetic mechanisms involving P2X7R activity in different autoimmune conditions. The possible involvement of P2X7R “loss of function” in Tfh cells in SLE and RA pathogenesis is indicated by a cross on P2X7R. Created with BioRender.