The role of the nuclear hormone receptor RORgammat in the development of lymph nodes and Peyer's patches

Abstract

The nuclear hormone receptor retinoic acid-related orphan receptor (ROR)gammat is required for the development of lymph nodes (LNs) and Peyer's patches (PPs), as these organs are absent in RORgammat-deficient mice. During fetal life, RORgammat is expressed exclusively in lymphoid tissue-inducer (LTi) cells, a cell type that localizes in developing LNs and PPs. LTi cells express surface lymphotoxin alpha1beta2 that activates specialized mesenchymal cells to produce chemokines, upregulate adhesion molecules and induce further maturation of lymphoid organs. RORgammat inhibits nuclear factor of activated T-cell (NFAT) function in cell lines and induces the expression of Bcl-xL and p27kip1 in the adult thymus, suggesting that RORgammat prevents cell activation, cell-cycle progression, and apoptosis. We propose that RORgammat, together with the inhibitor of basic helix-loop-helix transcription factor Id2, ensures generation and survival of fetal LTi cells necessary for the development of LNs and PPs.