P2RX7 Deletion in T Cells Promotes Autoimmune Arthritis by Unleashing the Tfh Cell Response

作者：Krysta M. Felix, Fei Teng, Nicholas A. Bates, Heqing Ma, Ivan A. Jaimez, Kiah C. Sleiman, Nhan L. Tran, Hsin-Jung Joyce Wu · 发表于：Frontiers in Immunology · 年份：2019 · DOI：10.3389/fimmu.2019.00411 · 被引用次数：17 · 研究领域：Immune Cell Function and Interaction、Adenosine and Purinergic Signaling、Immunodeficiency and Autoimmune Disorders

Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1% of the world’s population. B cells and autoantibodies play an important role in the pathogenesis of RA. The P2RX7 receptor is an ATP-gated cation channel and its activation results in the release of pro-inflammatory molecules. Thus, antagonists of P2RX7 have been considered to have potential as novel anti-inflammatory therapies. Although originally identified for its role in innate immunity, P2RX7 has recently been found to negatively control Peyer’s patches (PP) T follicular helper cells, which specialize in helping B cells, under homeostatic conditions. We have previously demonstrated that PP Tfh cells are required for the augmentation of autoimmune arthritis mediated by gut commensal segmented filamentous bacteria (SFB). Thus, we hypothesized that P2RX7 is required to control autoimmune disease by keeping the Tfh cell response in check. To test our hypothesis, we analyzed the impact of P2RX7 deficiency in vivo using both the original K/BxN autoimmune arthritis model and T cell transfers in the K/BxN system. We also examined the impact of P2RX7 ablation on autoimmune development in the presence of the gut microbiota SFB. Our data illustrate that contrary to exerting an anti-inflammatory effect, P2RX7 deficiency actually enhances autoimmune arthritis. Interestingly, SFB colonization can negate the difference in disease severity between WT and P2RX7-deficient mice. We further demonstrated that P2...