Impaired dendritic cell differentiation and maturation in the absence of C3.
Human monocytes can be differentiated into immature dendritic cells (DCs) in the presence of serum and cytokines. One of the main functions of immature DCs is to capture and process antigens. Following maturation, they differentiate into antigen presenting cells. The role of complement in the differentiation process from monocytes towards immature DCs remains elusive. Here we demonstrate that complement 3 (C3) has a regulatory impact on the expression of specific DC surface molecules and DC-derived cytokine production during DC differentiation. We isolated human adherent peripheral blood mononuclear cells, which were cultured in the presence of GM-CSF plus IL-4 in medium supplemented with normal human serum or C3 deficient serum. The lack of C3 during DC differentiation negatively impacted the expression of C-type lectin receptor DC-SIGN, the antigen presenting molecules HLA-DR and CD1a, and the costimulatory molecules CD80 and CD86. Further, the spontaneous production of IL-6 and IL-12 was reduced in the absence of C3. Moreover, the maturation of immature DCs in response to LPS challenge was impaired in the absence of C3 as evidenced by reduced MHC-II, co-stimulatory molecule expression as well as modulated IL-12 and TNF-alpha production. Collectively, our results provide evidence for a novel role of C3 as a critical cofactor in human DC differentiation and maturation.
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, Brazil.
Edimara S
ES
Reis
J A M
JA
Barbuto
Jörg
J
Köhl
Lourdes
L
Isaac
D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003176:Complement C3 / Q000172:deficiency* / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000276:immunology; D044967:Serum; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D018949:Antigens, CD1; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039521:CD11c Antigen; D015815:Cell Adhesion Molecules; D003176:Complement C3; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C419393:CD1a antigen