title: Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10032, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Melillo
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Blazquez
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Plumlee
authors.forename: Carolyn
authors.initials: C
authors.lastname: Lee
authors.forename: Cecilia
authors.initials: C
authors.lastname: Berin
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D008206:Lymphatic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma