Background AIRE is a transcription factor that is involved in the negative selection of self-reactive thymocytes in the thymus. Recently, AIRE protein has also been detected in peripheral lymphoid organs, predominantly in dendritic cells (DC). In these peripheral sites, AIRE was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus, suggesting that peripheral AIRE may play a complementary role in tolerance induction. It is currently unknown whether AIRE may play a role in inflamed tissues, such as rheumatoid arthritis (RA) synovial tissue (ST).
Objective To document and further characterise extrathymic AIRE expressing cells in ST and paired peripheral blood (PB) mononuclear cells (MCs) as well synovial fluid (SF) MCs of RA patients.
Methods ST was obtained via mini-arthroscopy from inflamed joints of RA or undifferentiated arthritis (UA) patients. Expression of AIRE was evaluated using IHC and IF microscopy. AIRE expression was also investigated in PB and SF DC using flow cytometry.
Results AIRE expressing cells were detected in 80% of analysed RA ST and in contrast only in 25% of UA ST. Further characterisation using double-immunofluorescence microscopy revealed that these cells were predominantly CD1c+ myeloid (m)DC. Interestingly, a significantly higher percentage of CD1c+ mDC in RA SF expressed AIRE (55 ± 5%) compared to RA PB (20 ± 3%) and healthy PB (19.7 ± 2%).
Conclusions Extrathymic AIRE expressing CD1c+ mDCs are present in RA ST and RA SF, suggesting a role in synovial inflammation. Extrathymic AIRE expression in RA synovial inflammation may be an attempt to control inflammation through the induction of peripheral tolerance to antigens involved in the perpetuation of the chronic inflammatory response.