Thymic keratin 76 regulates skin-specific central tolerance

Medullary thymic epithelial cells (mTECs) express tissue-specific antigens (TSAs) to educate developing T cells about self-antigens. Recent advances in single-cell technologies have revealed that mTECs differentiate into specialised mimetic cell subsets that co-opt lineage-defining transcription factors to express biologically coherent sets of TSAs.

Keratin intermediate filament proteins are expressed throughout the thymus but their roles in central tolerance remain unclear. Here we show that keratin 76 (Krt76) expressed in specialised mimetic mTECs controls skin-specific central tolerance by regulating the presentation of skin TSAs. Loss of Krt76 in the thymus leads to defective TEC differentiation, reduced skin-specific TSA expression, dysregulated T cell balance and development of skin autoimmunity in mice.