[Gd@C(82)(OH)(22)](n) nanoparticles induce dendritic cell maturation and activate Th1 immune responses.
Dendritic cells play a pivotal role in host immune defense, such as elimination of foreign pathogen and inhibition of tumorigenesis. In this paper, we report that [Gd@C(82)(OH)(22)](n) could induce phenotypic maturation of dendritic cells by stimulating DC production of cytokines including IL-12p70, upregulating DC co-stimulatory (CD80, CD83, and CD86) and MHC (HLA-A,B,C and HLA-DR) molecules, and switching DCs from a CCL5-responsive to a CCL19-responsive phenotype. We found that [Gd@C(82)(OH)(22)](n) can induce dendritic cells to become functionally mature as illustrated by their capacity to activate allogeneic T cells. Mice immunized with ovalbumin in the presence of [Gd@C(82)(OH)(22)](n) exhibit enhanced ovalbumin-specific Th1-polarized immune response as evidenced by the predominantly increased production of IFNgamma, IL-1beta, and IL-2. The [Gd@C(82)(OH)(22)](n) nanoparticle is a potent activator of dendritic cells and Th1 immune responses. These new findings also provide a rational understanding of the potent anticancer activities of [Gd@C(82)(OH)(22)](n) nanoparticles reported previously.
Yang
De
D
Tianjin Medical University, Research Center of Basic Medic Sciences, Cancer Institute and Hospital, Tianjin 300060, China.
Zhao
Yuliang
Y
Guo
Hua
H
Li
Yana
Y
Tewary
Poonam
P
Xing
Gengmei
G
Hou
Wei
W
Oppenheim
Joost J
JJ
Zhang
Ning
N
D000818:Animals; D000941:Antigens / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D037741:Fullerenes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; D000970:Antineoplastic Agents; D037741:Fullerenes; D015850:Interleukin-6; D009942:Organometallic Compounds; D005682:Gadolinium