 The immune system has the important job of recognizing and eliminating dangerous pathogens such as bacteria, viruses, or fungi, while recognizing the body's own cells and leaving them alone. When this self-recognition goes wrong, immune cells wreak havoc by attacking the body's own cells, causing autoimmune disease. Over the past several decades, researchers have worked to understand the activities of a special protein called air, a transcription regulator without which our immune system is unable to tell self-cells from invaders. Air works exclusively in a unique cell population of the thymus, where it turns on a battery of the body's own proteins. This in turn serves as a sort of test for newly generated T-cells, those that are self-reactive are eliminated so that they will not cause harm by attacking the body's own tissues when released to the circulation. Researchers have examined how air manages to express this mix of genes by studying a rare population of air-positive thymic cells called m-tex. The key seems to be in air's numerous binding partners and in its location. Air is found at the transcriptional start site of most genes, along with stalled RNA polymerase, too. Air is associated with silent chromatin, which allows it to act on genes that are off in most cell types and turn them on in m-tex. When stabilized, air promotes DNA breaks that result in the recruitment of DNA repair proteins and other air partners, ultimately activating transcription by opening up the chromatin around the target genes and releasing the stalled RNA polymerase. These events take place in unique air bodies that are associated with the nuclear matrix, which may serve to connect the proteins responsible for transcription with genes associated with air in hubs to support m-tex's unusual gene expression pattern. Although parts of this fascinating picture are coming into focus, much remains to be discovered. For example, researchers are trying to identify the specific factors that help open up the chromatin around air target genes. Better knowledge of these pathways may inform future therapies for autoimmune diseases.