AI Article Synopsis

  • APECED is a rare autoimmune disease caused by a malfunctioning gene called AIRE, which plays a crucial role in preventing autoimmune disorders by regulating immune tolerance to specific tissue antigens.
  • AIRE is primarily expressed in thymic cells, and its absence leads to a breakdown of tolerance, resulting in various autoimmune disorders, as shown in studies with mice lacking this gene.
  • Recent proteomic analyses revealed that AIRE-expressing cells have higher levels of certain chaperone proteins and lower levels of cytoskeletal proteins, along with changes in apoptosis-related proteins, indicating that AIRE influences cell stress responses and apoptosis rates.

Article Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive autoimmune disease, affecting many endocrine tissues. APECED is associated to the lack of function of a single gene called AutoImmune REgulator (AIRE). Aire knockout mice develop various autoimmune disorders affecting different organs, indicating that Aire is a key gene in the control of organ-specific autoimmune diseases. AIRE is mainly expressed by medullary thymic epithelial cells (mTECs), and its absence results in the loss of tolerance against tissue restricted antigens (TRAs). Aire induces the transcription of genes encoding for TRAs in mTECs. In this report, the analysis of AIRE's effect on the cellular proteome was approached by the combination of two quantitative proteomics techniques, 2D-DIGE and ICPL, using an AIRE-transfected and nontransfected epithelial cell line. The results showed increased levels of several chaperones, (HSC70, HSP27 and tubulin-specific chaperone A) in AIRE-expressing cells, while various cytoskeleton interacting proteins, that is, transgelin, caldesmon, tropomyosin alpha-1 chain, myosin regulatory light polypeptide 9, and myosin-9, were decreased. Furthermore, some apoptosis-related proteins were differentially expressed. Data were confirmed by Western blot and flow cytometry analysis. Apoptosis assays with annexin V and etoposide demonstrated that AIRE-positive cells suffer more spontaneous apoptosis and are less resistant to apoptosis induction.

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http://dx.doi.org/10.1021/pr100044dDOI Listing

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