Abstract
Peripheral T cells capable of discriminating between self and non-self antigens are major components of a robust adaptive immune system. The development of self-tolerant T cells is orchestrated by thymic epithelial cells (TECs), which are localized in the thymic cortex (cortical TECs, cTECs) and medulla (medullary TECs, mTECs). cTECs and mTECs are essential for differentiation, proliferation, and positive and negative selection of thymocytes. Recent advances in single-cell RNA-sequencing technology have revealed a previously unknown degree of TEC heterogeneity, but we still lack a clear picture of the identity of TEC progenitors in the adult thymus. In this review, we describe both earlier and recent findings that shed light on features of these elusive adult progenitors in the context of tissue homeostasis, as well as recovery from stress-induced thymic atrophy.
Highlights
Once regarded as a vestigial organ that had lost its function during evolution, the thymus is recognized as a primary lymphoid organ that performs irreplaceable functions in differentiation and selection of self-tolerant T cells [1]
This event is orchestrated by two types of thymic epithelial cells (TECs) that reside in the thymic cortex and medulla
It is most likely that mTEC progenitors and cTECs are derived from bipotent progenitors in the embryonic thymus, mechanisms underlying fate decisions of bipotent TEC progenitors remain elusive
Summary
Once regarded as a vestigial organ that had lost its function during evolution, the thymus is recognized as a primary lymphoid organ that performs irreplaceable functions in differentiation and selection of self-tolerant T cells [1]. Wong et al [26] proposed that bipotent progenitors are present in a subset of TECs expressing low levels of MHCII and LY51 and lacking the mTEC marker UEA-1 ligand (referred to as TEClo) They both found that bipotent progenitors were present in UEA1-negative TEC fractions, and that they express surface LY51 and Pax mRNA, suggesting their similarity to cTECs. there are some discrepancies between these studies. It may be possible that both unipotent cTEC and mTEC progenitors could be present in TEClo [25, 26] As both studies verified their differentiation potential using reaggregation with fetal thymic cells, such conditions may not be suitable to address adult progenitors. In vivo fate mapping needs to be performed in the adult thymus to evaluate their physiological fate
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