Direct and indirect roles of the LTβR pathway in central tolerance induction

Medullary thymic epithelial cells (mTECs) play a critical role in thymic negative selection of autoreactive thymocytes, especially for thymocytes specific for peripheral tissue-restricted self-antigens (TRA). Deficiency in lymphotoxin b receptor (LTβR) is associated with peripheral tissue inflammation, but whether this is caused by defective negative selection has been unclear; the significance of the LTβR pathway for negative selection is evident in some models but not others. Here, we revisit the data and clarify the role of LTβR in mTEC development and function and thymic TRA expression. These processes are discussed as potential mechanisms for LTβR-mediated control of negative selection.