Memory Th1/Th2 cell generation controlled by Schnurri-2.
Schnurri (Shn) is a large zinc-finger containingprotein, which plays a critical role in cell growth, signal transduction and lymphocyte development. There are three orthologues (Shn-1, Shn-2 and Shn-3) in vertebrates. In Shn-2-deficient mice, the activation of NF-kappaB in CD4 T cells is upregulated and their ability to differentiate into Th2 cells is enhanced in part through the increased expression of GATA3. Shn-2 is found to compete with p50 NF-kappaB for binding to a consensus NF-kappaB motif and inhibit the NF-kappaB-driven promoter activity. In addition, Th2-driven allergic airway inflammation was enhanced in Shn-2-deficient mice. Therefore, Shn-2 appears to negatively control the differentiation of Th2 cells and Th2 responses through the repression of NF-kappaB function. Memory Th1/Th2 cells are not properly generated from Shn-2-deficient effector Th1/Th2 cells. The expression levels of CD69 and the number ofapoptotic cells are selectively increased in Shn-2-deficient Thl/Th2 cells when they are transferred into syngeneic host animals, in which memoryh Th1/Th2 cells are generated within a month. In addition, an increased susceptibility to apoptotic cell death is also observed in vitro accompanied with the increased expression of FasL, one of the NF-kappaB-dependent genes. Th2 effector cells overexpressing the p65 subunit of NF-kappaB demonstrate a decreased cell survival particularly in the lymph node. These results indicate that Shn-2-mediated repression of NF-kappaB is required for cell survival and the successful generation of memory Th1/Th2 cells. This may point to the possibility that after antigen clearance the recovery of the quiescent state in effector Th cells is required for the generation of memory Th cells. A repressor molecule Shn-2 plays an important role in this process.
Nakayama
Toshinori
T
Department of Immunology, Graduate School of Medicine, Chiba University, Japan. tnakayama@faculty.chiba-u.jp
Kimura
Motoko Y
MY
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D005810:Multigene Family; D016328:NF-kappa B / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D016328:NF-kappa B