Gene Set: GSE40225_WT_VS_RIP_B7X_DIABETIC_MOUSE_PANCREATIC_CD8_TCELL_DN

Standard name GSE40225_WT_VS_RIP_B7X_DIABETIC_MOUSE_PANCREATIC_CD8_TCELL_DN
Systematic name M9240
Brief description Genes down-regulated in pancreatic CD8 T cells from mice with: type 1 diabetes mellitus versus healthy controls.
Full description or abstract B7x (B7-H4 or B7S1) is the seventh member of the B7 family and the in vivo function remains largely unknown. Despite new genetic data linking the B7x gene with autoimmune diseases, how exactly it contributes to peripheral tolerance and autoimmunity is unclear. Here we showed that B7x protein was not detected on antigen-presenting cells or T cells in both human and mice, which is unique in the B7 family. As B7x protein is expressed in some peripheral cells such as pancreatic b cells, we utilized a CD8 T cell-mediated diabetes model (AI4ab) in which CD8 T cells recognize an endogenous self-antigen, and found that mice lacking B7x developed more severe diabetes than control AI4ab mice. Conversely, mice overexpressing B7x in the b cells (Rip-B7xAI4ab) were diabetes free. Furthermore, adoptive transfer of effector AI4ab CD8 T cells induced diabetes in control mice, but not in Rip-B7xAI4ab mice. Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of migrating to the pancreas but failed to robustly destroy tissue when encountering local B7x in Rip-B7xAI4ab mice. Although AI4ab CD8 T cells in Rip-B7xAI4ab mice and AI4ab mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in AI4ab mice than in RIP-B7xAI4ab mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells and that local overexpression of B7x on pancreatic b cells is sufficient to abolish CD8 T cell-induced diabetes.
Collection C7: immunologic signature gene sets
      IMMUNESIGDB: ImmuneSigDB gene sets
Source publication Pubmed 22972920   Authors: Lee JS,Scandiuzzi L,Ray A,Wei J,Hofmeyer KA,Abadi YM,Loke P,Lin J,Yuan J,Serreze DV,Allison JP,Zang X
Exact source GSE40225_3063_200_DN
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Organism Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform HUMAN_GENE_SYMBOL
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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