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Publication : Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function.

First Author  Melillo JA Year  2010
Journal  J Immunol Volume  184
Issue  5 Pages  2638-45
PubMed ID  20124100 Mgi Jnum  J:159650
Mgi Id  MGI:4452200 Doi  10.4049/jimmunol.0902960
Citation  Melillo JA, et al. (2010) Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function. J Immunol 184(5):2638-45
abstractText  Dendritic cells (DCs) must achieve a critical balance between activation and tolerance, a process influenced by cytokines and growth factors. IL-10, which transduces signals through Stat3, has emerged as one important negative regulator of DC activation. To directly examine the role Stat3 plays in regulating DC activity, the Stat3 gene was targeted for deletion with a CD11c-cre transgene. Stat3 CKO mice developed cervical lymphadenopathy as well as a mild ileocolitis that persisted throughout life and was associated with impaired weight gain. Consistent with this, Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. These results reveal a cell-intrinsic negative regulatory role of Stat3 in DCs and link increased DC activation with perturbed immune homeostasis and chronic mucosal inflammation.
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