Increased circulating CD11b+CD11c+ dendritic cells (DC) in aged BWF1 mice which can be matured by TNF-alpha into BLC/CXCL13-producing DC.
Dendritic cells (DC) play a pivotal role in regulating immune responses. We previously reported aberrant high production of B lymphocyte chemoattractant (BLC/CXCL13) by DC in aged BWF1 mice, amurine model for systemic lupus erythematosus (SLE). We describe here that CD11b+CD11c+ cells were markedly increased in the peripheral blood (PBL-DC) in aged BWF1, but not in similarly aged NZB or NZW mice. Part of PBL-DC showed a typical dendritic morphology and expressed MHC class II molecules, and had a weak, but significant antigen-presenting ability in mixed lymphocytereaction. PBL-DC were chemoattracted to several chemokines in vitro including secondary lymphoid tissue chemokine (SLC), liver and activation-regulated chemokine (LARC), RANTES, macrophage inflammatory protein-1alpha, whereas splenic mature DC from aged BWF1 mice were preferentially chemoattracted towards SLC. BLC production was induced when PBL-DC were cultured in the presence of TNF-alpha for 3 days. BLC expression was also induced in bone marrow-derived DC when they were differentiated into mature DC in the presence of TNF-alpha and IL-1beta, while both IFN-alpha and IFN-gamma failed to induce BLC expression in bone marrow-derived DC. Since TNF-alpha expression is increased in aged BWF1 mice, DC recruitment in the circulation and maturation into BLC-producing DC by TNF-alpha may play a pivotal role in the development of systemic autoimmune diseases.
Ishikawa
Sho
S
Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan.
Nagai
Shigenori
S
Sato
Taku
T
Akadegawa
Kenji
K
Yoneyama
Hiroyuki
H
Zhang
Yan-Yun
YY
Onai
Nobuyuki
N
Matsushima
Kouji
K
D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015415:Biomarkers; D002454:Cell Differentiation; D002478:Cells, Cultured; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D016167:Integrin alphaXbeta2 / Q000276:immunology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007958:Leukocyte Count; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
D015415:Biomarkers; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D016167:Integrin alphaXbeta2; D016898:Interferon-alpha; D007375:Interleukin-1; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma