[PDF][PDF] Differential roles of IL-2 signaling in developing versus mature Tregs

MY Fan, JS Low, N Tanimine, KK Finn… - Cell reports, 2018 - cell.com
MY Fan, JS Low, N Tanimine, KK Finn, B Priyadharshini, SK Germana, SM Kaech, LA Turka
Cell reports, 2018cell.com
Although Foxp3+ regulatory T cells (Tregs) require interleukin-2 (IL-2) for their development,
it has been unclear whether continuing IL-2 signals are needed to maintain lineage stability,
survival, and suppressor function in mature Tregs. We generated mice in which CD25, the
main ligand-binding subunit of the IL-2 receptor, can be inducibly deleted from Tregs after
thymic development. In contrast to Treg development, we find that IL-2 is dispensable for
maintaining lineage stability in mature Tregs. Although continuous IL-2 signaling is needed …
Summary
Although Foxp3+ regulatory T cells (Tregs) require interleukin-2 (IL-2) for their development, it has been unclear whether continuing IL-2 signals are needed to maintain lineage stability, survival, and suppressor function in mature Tregs. We generated mice in which CD25, the main ligand-binding subunit of the IL-2 receptor, can be inducibly deleted from Tregs after thymic development. In contrast to Treg development, we find that IL-2 is dispensable for maintaining lineage stability in mature Tregs. Although continuous IL-2 signaling is needed for long-term Treg survival, CD25-deleted Tregs may persist for several weeks in vivo using IL-7. We also observe defects in glycolytic metabolism and suppressor function following CD25 deletion. Thus, unlike developing Tregs in which the primary role of IL-2 is to initiate Foxp3 expression, mature Tregs require continuous IL-2 signaling to maintain survival and suppressor function, but not to maintain lineage stability.
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