Requirement for POH1 in differentiation and maintenance of regulatory T cells

摘要

Foxp3-expressing regulatory T (Treg) cells are essential for averting autoimmune diseases and maintaining immune homeostasis. However, the molecular mechanisms underlying the development and maintenance of Treg cells are still unclear. Here, we found that T cell-specific deletion of the gene encoding the deubiquitinase POH1 compromised the development of mature T cells, especially CD4(+) Foxp3(+) Treg cells. Moreover, POH1 deficiency significantly attenuated the transition of CD25(+) Treg cell precursors into Foxp3(+) Treg cells accompanied by downregulation of interleukin 2 (IL-2)-STAT5 signaling. Deletion of POH1 in generated CD4(+)Foxp3(+) Treg cells led to an early onset of fetal autoimmune disorders and a decrease in the pool size of peripheral Treg cells in mice, which were mostly due to decreased expansion of these cells. Thus, these results revealed that POH1 has a pivotal role in the development and maintenance of CD4(+)Foxp3(+) Treg cells and contributes to immune tolerance.