Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium
Jiaxi Wang, Caleb A. Lareau, Jhoanne L. Bautista, Alexander R. Gupta, Katalin Sándor, Joe Germino, Yajie Yin, Matthew P. Arvedson, Gabriella C. Reeder, Nathan T. Cramer, Fang Xie, Vasilis Ntranos, Ansuman T. Satpathy, Mark S. Anderson, James M. Gardner
Abstract
migratory dendritic cells. eTACs, particularly JCs, have highly accessible chromatin and broad gene expression, including a range of tissue-specific antigens, as well as remarkable homology to medullary thymic epithelium and RANK-dependent Aire expression. Transgenic self-antigen expression by eTACs is sufficient to induce negative selection and prevent autoimmune diabetes. This transcriptional, genomic, and functional symmetry between eTACs (both JCs and AmDCs) and medullary thymic epithelium—the other principal Aire-expressing population and a key regulator of central tolerance—identifies a core program that may influence self-representation and tolerance across the spectrum of immune development.