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Effect of Mucosal Cytokine Administration on Selective Expansion of Vaginal Dendritic Cells to Support Nanoparticle Transport
Author(s) -
Ramanathan Renuka,
Park Jaehyung,
Hughes Sean M.,
Lykins William R.,
Bennett Hunter R.,
Hladik Florian,
Woodrow Kim A.
Publication year - 2015
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12409
Subject(s) - chemokine , immunology , immune system , dendritic cell , ccl20 , cytokine , antigen presenting cell , inflammation , integrin alpha m , antigen , population , granulocyte macrophage colony stimulating factor , biology , medicine , t cell , chemokine receptor , environmental health
Problem The capacity of antigen‐carrying vaccine nanoparticles ( NP s) administered vaginally to stimulate local immune responses may be limited by the relatively low numbers of antigen‐presenting cells ( APC s) in the genital mucosa. Because inflammation is associated with increased susceptibility to sexually transmitted infections, we sought to increase APC numbers without causing inflammation. Method of Study In this study, we evaluated intravaginal delivery of chemokines, growth factors, or synthetic adjuvants to expand APC s in reproductive tissues. Results We found that granulocyte–macrophage colony‐stimulating factor ( GM ‐ CSF ) stimulated expansion of CD 11b+ dendritic cells (DCs) within 24 hr of intravaginal administration, with no effect on Langerhans cells or macrophages. Expansion of the CD 11b+ DC population was not associated with increased inflammatory cytokine production, and these cells retained phagocytic function. Conclusion Our data suggest that non‐inflammatory expansion of mucosal APC s by intravaginal GM ‐ CSF could be used as an adjuvanting strategy to potentiate the genital immune response to nanoparticulate mucosal vaccines.