Transcriptional and translational control of Foxp3+ regulatory T cell functional adaptation to inflammation.

Piccirillo, Ciriaco A

Foxp3+ regulatory T (Treg) cells are the major gatekeepers of the immune system for the maintenance of self-tolerance and immune homeostasis. Treg cell development rests on the key activities of the master-switch transcription factor, Foxp3, which establishes the essential core program that defines Treg cell lineage identity in the thymus and peripheral tissues. Moreover, Foxp3+ Treg cells integrate a variety of inflammatory signals from the tissue microenvironment to engage specialized pathways in order to adapt their suppressive functions in situ. CD4 + Treg cell subsets possess mechanisms to control both gene transcription and mRNA translation. Ultimately, the resulting proteome orchestrates distinct cellular processes that poise Treg cell subsets to respond to inflammatory signals in a timely and context-dependent manner in lymphoid and non-lymphoid tissues for a coordinated modulation of immunity. Thus, understanding how Treg cells control their cellular adaptation in lymphoid and non-lymphoid tissues may reveal therapeutic targets for the treatment of autoimmunity and chronic inflammatory diseases.