The autoimmune regulator (Aire) is essential for prevention of autoimmunity; its role is best understood in the thymus, where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4⁺ T cells through a mechanism that does not require regulatory T cells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804105 | PMC |
| http://dx.doi.org/10.1016/j.immuni.2013.08.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A deep intronic splice-altering variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion.
Sci Transl Med
September 2024
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Article Synopsis
- APECED is a serious genetic autoimmune disorder linked to variants in the autoimmune regulator (AIRE) gene, with 16% of evaluated patients lacking known harmful variants, most of whom are of Puerto Rican descent.
- Researchers discovered a deep intronic variant (c.1504-818 G>A) in these patients that causes a cryptic splice site leading to a dysfunctional protein through pseudoexon inclusion.
- They developed an antisense oligonucleotide (ASO) that corrected this genetic issue, demonstrating the potential for targeted treatments in APECED patients.
Extrathymic AIRE-Expressing Cells: A Historical Perspective.
Adv Exp Med Biol
March 2024
Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Since its discovery, Aire has been the topic of numerous studies in its role as a transcriptional regulator in the thymus where it promotes the "promiscuous" expression of a large repertoire of tissue-restricted antigens (TRAs) that are normally expressed only in the immune periphery. This process occurs in specialized medullary thymic epithelial cells (mTECs) and mediates the elimination of self-reactive T cells or promotes their conversion to the Foxp3 regulatory T cell lineage, both of which are required for the prevention of autoimmunity. In recent years, there has been increasing interest in the role of extrathymic Aire expression in peripheral organs.
View Article and Find Full Text PDFDevelopmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium.
Elife
March 2024
Thymus Biology Section, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla.
View Article and Find Full Text PDFAire in Autoimmunity.
Annu Rev Immunol
June 2024
Diabetes Center, University of California, San Francisco, California, USA; email:
Article Synopsis
- The autoimmune regulator (Aire) was first identified over 20 years ago, playing a crucial role in central immune tolerance and thymic self-representation, and recent advancements in single-cell genomics are revealing new insights about its biology.
- The text discusses how human genetics helped discover Aire and how various patient data related to Aire mutations sheds light on its link to autoimmune diseases and implications for health.
- It also highlights three key areas of emerging research: the diversity of medullary thymic epithelial cells and Aire's role in their development, the molecular mechanisms of Aire and its partners, and the identification and function of extrathymic Aire-expressing cells, including a new type called Janus cells, crucial for maintaining immune
Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium.
bioRxiv
December 2023
Thymus Biology Section, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!