Antigen-presenting cells (APCs) are master regulators of the immune response by directly interacting with T cells to orchestrate distinct functional outcomes. Several types of professional APC exist, including conventional dendritic cells, B cells and macrophages, and numerous other cell types have non-classical roles in antigen presentation, such as thymic epithelial cells, endothelial cells and granulocytes. Accumulating evidence indicates the presence of a new family of APCs marked by the lineage-specifying transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and demonstrates that these APCs have key roles in shaping immunity, inflammation and tolerance, particularly in the context of host-microorganism interactions. These RORγt+ APCs include subsets of group 3 innate lymphoid cells, extrathymic autoimmune regulator-expressing cells and, potentially, other emerging populations. Here, we summarize the major findings that led to the discovery of these RORγt+ APCs and their associated functions. We discuss discordance in recent reports and identify gaps in our knowledge in this burgeoning field, which has tremendous potential to advance our understanding of fundamental immune concepts.

Department of Cell Biology Faculty of Science Charles University Prague Czech Republic

Department of Immunology and Regenerative Biology Weizmann Institute of Science Rehovot Israel

Department of Microbiology and Immunology Weill Cornell Medicine Cornell University New York NY USA

Jill Roberts Institute for Research in Inflammatory Bowel Disease Weill Cornell Medicine Cornell University New York NY USA

Joan and Sanford 1 Weill Department of Medicine Division of Gastroenterology and Hepatology Weill Cornell Medicine Cornell University New York NY USA

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Extrathymic AIRE-Expressing Cells: A Historical Perspective