Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function.
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.
Melillo
Jessica A
JA
Department of Biological Sciences, Columbia University, New York, NY 10032, USA.
Song
Li
L
Bhagat
Govind
G
Blazquez
Ana Belen
AB
Plumlee
Courtney R
CR
Lee
Carolyn
C
Berin
Cecilia
C
Reizis
Boris
B
Schindler
Christian
C
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
D039521:CD11c Antigen; D016207:Cytokines; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma