Aire-expressing ILC3-like cells in the lymph node display potent APC features

Area of Science:

• Immunology
• Cell Biology
• T cell tolerance

Background:

• The autoimmune regulator (Aire) is crucial for T cell tolerance by inducing tissue antigen expression in thymic epithelial cells.
• Aire is also found in rare cells in peripheral lymphoid organs, but their identity and function remain unclear.

Purpose of the Study:

• To identify and characterize Aire-expressing cells in peripheral lymph nodes.
• To investigate the functional properties of these cells in the context of immune regulation.

Main Methods:

• Flow cytometry and transcriptional profiling to identify Aire+ cells in lymph nodes.
• Assessment of cell morphology, lineage marker expression, and RORγt dependence.
• Analysis of surface molecule expression (MHCII, costimulatory molecules) and antigen presentation capacity.
• Comparison of Aire+ cell frequency in different lymph node types.

Main Results:

• Aire-expressing cells in lymph nodes exhibit characteristics of group 3 innate lymphoid cells (ILC3s), including lymphoid morphology and RORγt dependence.
• These Aire+ ILC3-like cells express high levels of MHCII and costimulatory molecules.
• They demonstrate potent antigen-presenting cell (APC) capabilities, efficiently presenting endogenous antigens to CD4+ T cells.
• Aire+ cells are more prevalent in peripheral lymph nodes compared to mucosa-draining lymph nodes and possess a unique Aire-dependent transcriptional signature.

Conclusions:

• This study defines a novel subset of ILC3-like cells expressing Aire in peripheral lymphoid organs.
• These cells possess potent APC functions, suggesting a previously unrecognized role in modulating T cell responses and maintaining peripheral tolerance.