英国剑桥大学Arthur Kaser团队发现，一个嘌呤代谢的检查点可阻止自身免疫和自身炎症。2022年1月4日出版的《细胞—代谢》杂志发表了这项成果。

Title: A purine metabolic checkpoint that prevents autoimmunity and autoinflammation

Author: Svetlana Saveljeva, Gavin W. Sewell, Katharina Ramshorn, M. Zaeem Cader, James A. West, Simon Clare, Lea-Maxie Haag, Rodrigo Pereira de Almeida Rodrigues, Lukas W. Unger, Ana Belén Iglesias-Romero, Lorraine M. Holland, Christophe Bourges, Muhammad N. Md-Ibrahim, James O. Jones, Richard S. Blumberg, James C. Lee, Nicole C. Kaneider, Trevor D. Lawley, Allan Bradley, Gordon Dougan, Arthur Kaser

Issue&Volume: 2022/01/04

Abstract: Still’s disease, the paradigm of autoinflammation-cum-autoimmunity, predisposes for a cytokine storm with excessive T lymphocyte activation upon viral infection. Loss of function of the purine nucleoside enzyme FAMIN is the sole known cause for monogenic Still’s disease. Here we discovered that a FAMIN-enabled purine metabolon in dendritic cells (DCs) restrains CD4+ and CD8+ T cell priming. DCs with absent FAMIN activity prime for enhanced antigen-specific cytotoxicity, IFNγ secretion, and T cell expansion, resulting in excessive influenza A virus-specific responses. Enhanced priming is already manifest with hypomorphic FAMIN-I254V, for which ～6% of mankind is homozygous. FAMIN controls membrane trafficking and restrains antigen presentation in an NADH/NAD+-dependent manner by balancing flux through adenine-guanine nucleotide interconversion cycles. FAMIN additionally converts hypoxanthine into inosine, which DCs release to dampen T cell activation. Compromised FAMIN consequently enhances immunosurveillance of syngeneic tumors. FAMIN is a biochemical checkpoint that protects against excessive antiviral T cell responses, autoimmunity, and autoinflammation.

DOI: 10.1016/j.cmet.2021.12.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00628-8