Journal
FASEB JOURNAL
Volume 35, Issue 5, Pages -Publisher
WILEY
DOI: 10.1096/fj.202100139R
Keywords
CD74 (invariant chain); maturation; medullary thymic epithelial cells (mTECs); NF-kappa b; thymic epithelial cells (TECs)
Categories
Funding
- National Natural Science Foundation of China [81801390, 81871712, 31800754]
- National Key Research and Development Program of China [2017YFA0105002, 2017YFA0104402]
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CD74 plays a crucial role in regulating the development of medullary thymic epithelial cells (mTECs) in the thymus, positively controlling mTEC cellularity and maturation partially through activation of the canonical NF-kappa B signaling pathway.
Thymic epithelial cells (TECs) are indispensable for T cell development, T cell receptor (TCR) repertoire selection, and specific lineage differentiation. Medullary thymic epithelial cells (mTECs), which account for the majority of TECs in adults, are critical for thymocyte selection and self-tolerance. CD74 is a nonpolymorphic transmembrane glycoprotein of major histocompatibility complex class II (MHCII) that is expressed in TECs. However, the exact role of CD74 in regulating the development of mTEC is poorly defined. In this research, we found that loss of CD74 resulted in a significant diminution in the medulla, a selective reduction in the cell number of mature mTECs expressing CD80 molecules, which eventually led to impaired thymic CD4(+) T cell development. Moreover, RNA-sequence analysis showed that CD74 deficiency obviously downregulated the canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling pathway in mTECs. Our results suggest that CD74 positively controls mTEC cellularity and maturation partially by activating the canonical NF-kappa B signaling pathway.
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