In physiologic conditions, the concentration of eATP is quite low but it can be rapidly released in various amounts after cell stress, damage or death. Then, eATP exerts immunostimulatory or immunosuppressive effects depending on its extracellular concentration, on which P2 receptors are engaged on specific immune cells and on the extent of the stimulation. Roughly, murine models of inflammatory and autoimmune diseases have shown that eATP can act as a proinflammatory molecule not only by stimulating innate immune responses but also by favoring effector T-cell activation, mainly through P2X7 signaling. In our work, by using a specific gene knockout approach, we have focused on the SAR131675 effect of eATP on P2Y2R instead of using receptor specific antagonists. However, it is likely that other P2 receptors, including P2X receptors might also play a role in EAU development. In this context, two studies reported contradictory effect of P2X7 deficiency on experimental autoimmune encephalomyelitis development, either protective or deleterious. Yet, It has been shown also that the nucleotide affinity for P2Y2 receptors is significantly higher than for P2X7 receptors In humans, several in vitro studies have pointed out a more complex role of eATP, able also to inhibit the cytokine secretion, proliferation or cytotoxic activity of immune cells such as DC, macrophages, NK cells and T lymphocytes through the activation of P2Y11 receptors. Those P2Y11 receptors are however not expressed on murine cells. Another major fact to point out is that nucleotides are unstable short-lived molecules acting in an autocrine or paracrine manner. Especially, eATP is hydrolyzed into ADP/AMP and adenosine by plasma membranebound ectoenzymes, i.e. CD39 and CD73, whose expression on different immune cells or even on a same cell subset but in different location is quite variable. Therefore, a lot of studies evaluating the effect of eATP were done with ATPγS, a non-hydrolysable ATP analogue, rendering those data not comparable to ours. To our knowledge, there is no other publication on the role of the P2Y2 deficiency during the development of an experimental autoimmune disease. In order to evaluate a potential role of P2Y2R deficiency in lymphocyte migration, we similarly transferred Indium-radiolabeled TL and followed their in vivo migration with a SPECT camera. Unfortunately, this methodology appeared not sensitive enough to detect the presence of a small number of autoreactive TL in the eye. Besides, our findings are in line with several studies showing the importance of P2Y2R expression on epithelial and endothelial cells for VCAM1 expression and secondary recruitment of inflammatory cells. Altogether our results are in agreement with the present literature showing the DAMPs properties of nucleotides. Hence, Idzko M et al have shown that extracellular ATP triggers and maintains asthmatic airway Th2 inflammation and Granstein RD et al have demonstrated that ATPγS enhances cutaneous Th1 immune response. However, our data showed that the DC migration toward secondary lymphoid organs was not influenced by P2Y2R deficiency.