We investigated the expression of MOG and other central nervous system (CNS) antigens in human thymic epithelial cells (TECs) through an unbiased comparative approach.

Myelin oligodendrocyte glycoprotein (MOG) is predominantly expressed within the central nervous system, and disruption of central or peripheral tolerance towards MOG protein plays a crucial role in the autoimmune response to MOG. Promiscuous gene expression in medullary TECs (mTECs), particularly through AIRE expression, plays a key role in establishing central tolerance. The expression of central nervous system antigens (i.e. MOG and AQP4) in human TECs has not been extensively studied.

In this study, we conducted an analysis of two human thymus stromal single-cell RNA sequencing datasets (Bautista et al. and Park et al.) to compare the expression of MOG with that of other CNS antigens, namely AQP4, MBP, and PLP1 in different TECs.

Eleven clusters are identified in this combined dataset. Cortical TECs (cTEC: cTEC hi, cTEC lo, early cTEC, early cTEC+immature TEC), medullary TECs (mTEC: mTEC lo, AIRE+ mTEC hi, corneo-like mTEC, neuroendocrine+ mTEC), immature thymic epithelial cells (early cTEC+immature TEC, immature TEC/mcTEC), ciliated, and myoid cells are identified as described earlier in the Bautista et al dataset.

In this analysis, MOG expression was very low, only detected in a few cells. AQP4 transcripts were detected more frequently in the mTECs compared to MOG and concentrated in AIRE+ mTEC hi, corneo-like mTEC, neuroendocrine+ mTEC cells. PLP1 and MBP expression was readily detected in all clusters with higher expression found in cTECs and neuroendocrine+ mTECs. In contrast, insulin (INS), a known tissue specific antigen (TSA), was most abundant in AIRE+ mTEC hi and corneo-like mTEC clusters.