Like admirable diplomats, dendritic cells (DCs) smooth out wrinkles to establish peace when conflict isn't warranted. One way these antigen-presenting cells thwart attack is by equilibrating regulatory T (T reg) cell numbers, show Darrasse-Jèze and colleagues. In addition to other processes, like triggering T cell deletion and anergy, DC maintenance of T reg cell homeostasis is a newly recognized way for DCs to maintain tolerance in the immune system.

DC and T reg cell numbers rose and fell together in mice, according to the study. When DC numbers increased in response to injection with the DC-expanding cytokine Flt3 ligand (FL), T reg cells followed suit by proliferating. Without class II MHC molecules, however, a boost in DC numbers did not trigger T reg cell proliferation, suggesting that TCR stimulation is critical for DC-induced T reg cell expansion.

Conversely, when DC numbers were decreased, as occurs in FL-deficient mice, T reg cell counts were also low. Because of this effect, mice with type I diabetes and inflammatory bowel disorder fared poorly when their DCs were depleted, as protective T reg cells numbers also dropped. The paucity of T reg cells allowed Th1 and Th17 cell numbers to rise and exacerbate inflammation, and T reg cell injections then remedied symptoms of disease.

By showing that T reg cell numbers echo fluctuations in DC numbers, the authors round out their earlier findings that T reg cell depletion increases DCs by increasing FL production. The boost in DC numbers then expanded T reg cells, according to this study. Finally, T reg cell accumulation might induce cytokines that decrease DC numbers, although this link remains speculative. This give-and-take between DCs and T reg cells likely keeps the immune system balanced to prevent autoimmunity.