| First Author | Campbell IK | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 9 | Pages | 5468-77 |
| PubMed ID | 21421852 | Mgi Jnum | J:172752 |
| Mgi Id | MGI:5008698 | Doi | 10.4049/jimmunol.1002923 |
| Citation | Campbell IK, et al. (2011) Differentiation of inflammatory dendritic cells is mediated by NF-kappaB1-dependent GM-CSF production in CD4 T cells. J Immunol 186(9):5468-77 |
| abstractText | Rel/NF-kappaB transcription factors regulate inflammatory and immune responses. Despite possible subunit redundancy, NF-kappaB1-deficient (Nfkb1(-/-)) mice were profoundly protected from sterile CD4 T cell-dependent acute inflammatory arthritis and peritonitis. We evaluated CD4 T cell function in Nfkb1(-/-) mice and found increased apoptosis and selectively reduced GM-CSF production. Apoptosis was blocked by expression of a Bcl-2 transgene without restoring a disease response. In contrast with wild-type cells, transfer of Nfkb1(-/-) or GM-CSF-deficient CD4 T cells into RAG-1-deficient (Rag1(-/-)) mice failed to support arthritis induction. Injection of GM-CSF into Nfkb1(-/-) mice fully restored the disease response, suggesting that T cells are an important source of GM-CSF during acute inflammation. In Ag-induced peritonitis, NF-kappaB1-dependent GM-CSF production in CD4 T cells was required for disease and for generation of inflammatory monocyte-derived dendritic cells (MoDC), but not conventional dendritic cells. MoDC were identified in inflamed synovium and draining lymph nodes during arthritis. These MoDC produced high levels of MCP-1, a potent chemoattractant for monocytes. This study revealed two important findings: NF-kappaB1 serves a critical role in the production of GM-CSF by activated CD4 T cells during inflammatory responses, and GM-CSF derived from these cells drives the generation of MoDC during inflammatory disease. |
