1. Extrathymic AIRE-expressing cells: Friends or foes in autoimmunity and cancer?
- Author
-
van Laar, Gustaaf G., van Hamburg, Jan Piet, and Tas, Sander W.
- Subjects
- *
LYMPHOID tissue , *ANTIGEN presenting cells , *AUTOIMMUNITY , *INNATE lymphoid cells , *HOMEOSTASIS , *T cell receptors - Abstract
Auto-immune regulator (AIRE) is a transcription factor that is mainly known for its crucial role in the thymus. Here, AIRE ensures central tolerance by promoting the expression of peripheral tissue antigens in thymic epithelial cells, which is essential for the negative selection of autoreactive T cells. Intriguingly, AIRE expressing cells have recently been identified in other tissues outside the thymus as well. However, the exact function of these extrathymic AIRE expressing cells (eTACs) remains largely enigmatic. Human eTACs are mainly found in secondary lymphoid tissues under homeostatic conditions, but are also found in pathologies such as the inflamed tissues of patients with autoimmune diseases and in various cancer tissues. eTACs have been demonstrated to express dendritic cell (DC)-like markers, such as MHCII, CD40 and CD127, but also CCR7, IDO and PD-L1. Interestingly, eTACs lack high expression of co-stimulatory molecules, such as CD80 or CD86. In mice, different types of peripheral AIRE expressing cells have been described, including cells with an innate lymphoid cell-like phenotype and antigen presenting cell (APC) function. These findings suggest that eTACs are APCs with the possibility to modulate or inhibit immune responses, which is confirmed by functional murine studies demonstrating the ability of eTACs to induce tolerance in autoreactive T cells. The potential immunomodulatory function of eTACs makes them promising targets to restore tolerance in autoimmunity or improve immunotherapy in cancer settings. Yet, this requires a better understanding of these cells and the molecular mechanisms involved. In this review we aim to summarize the current knowledge and understanding of eTACs, including their putative roles in health and disease. • eTACs are found in secondary lymphoid tissues, inflamed tissues within autoimmunity and in various cancer tissues. • eTACs appear to be antigen presenting cells with the possibility to inhibit or modulate immune responses. • eTAC function plays a role in peripheral immunotolerance and may fall short in autoimmunity. • AIRE expression in malignant cells might aid these cells in immune evasion. • Extrathymic AIRE expression might be used in novel therapeutic strategies to combat both autoimmunity and malignancies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF