Plasticity and cell type-specific function of OTUB1 in infection (A05)

A05定义去泛素酶(DUB)CyLD通过抑制保护性信号通路而加重李斯特菌病，而DUB A20通过促进CD8+记忆T细胞的生存来改善李斯特菌病。利用新建立的条件OTUB1-/-小鼠品系，A05发现DUB OTUB1调节JAK-、TLR11-和YB-1介导的信号转导。在下一个资助期，A05将专注于李斯特菌病中(1)T细胞、(2)DC、(3)巨噬细胞和(4)肝细胞中的OTUB1，以确定OTUB1在炎症条件下的特定细胞类型的分子功能(与B19、B26协同)和可塑性(与A01、A04、A30N、Z01协同)。

A05 defined that the deubiquitinating enzyme (DUB) CYLD aggravates listeriosis by inhibiting protective signaling pathways, whereas the DUB A20 ameliorates listeriosis by enabling the survival of CD8+ memory T cells. Employing a newly established conditional OTUB1-/- mouse strain, A05 identified that the DUB OTUB1 regulates JAK-, TLR11- and YB-1-mediated signaling. In the next funding period, A05 will focus on OTUB1 in (1) T cells, (2) DCs, (3) macrophages and (4) hepatocytes in listeriosis to determine the cell type-specific molecular function (cooperation with B19, B26) and plasticity (cooperation with A01, A04, A30N, Z01) of OTUB1 under inflammatory conditions.